<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-4.4924pt" id="M1" height="16.753pt" version="1.1" viewBox="-0.0657574 -12.2606 17.9242 16.753" width="17.9242pt"><g transform="matrix(.017,0,0,-0.017,0,0)"><path id="g50-225" d="M493 373C493 420 472 451 445 451C421 451 400 435 400 410C400 404 402 400 406 394S417 371 417 350C417 259 317 128 256 55H254C260 126 256 262 238 340C219 424 194 451 163 451C128 451 78 413 24 329L52 302C89 353 106 370 121 370C129 370 137 363 147 336C186 231 196 73 184 -16C152 -88 120 -192 112 -238L130 -257C157 -253 213 -227 231 -213C231 -187 234 -77 240 -23C251 -6 277 30 309 69C424 208 493 299 493 373Z"/></g><g transform="matrix(.017,0,0,-0.017,8.721,0)"><path id="g50-226" d="M501 517C491 587 426 710 310 710C240 710 175 662 175 601C175 561 201 517 250 452C219 438 187 423 157 404C88 360 24 280 24 178C24 71 90 -12 195 -12C250 -12 297 6 334 32C412 87 452 170 452 249C452 335 408 396 333 481C259 565 229 601 229 621C229 642 245 652 275 652C359 652 427 583 490 499L501 517ZM364 233C364 142 323 33 222 33C173 33 119 81 119 178C119 265 156 335 193 374C213 395 242 413 272 425C308 384 364 319 364 233Z"/></g></svg> T Cell and Other Immune Cells Crosstalk in Cellular Immunity

He, Ying; Wu, Kangni; Hu, Yongxian; Sheng, Lixia; Tie, Ruxiu; Wang, Binsheng; Huang, He

doi:https://doi.org/10.1155/2014/960252

Journal of Immunology Research

On this page

Abstract Introduction Acknowledgments References Copyright Related Articles

Review Article | Open Access

Volume 2014 | Article ID 960252 | https://doi.org/10.1155/2014/960252

T Cell and Other Immune Cells Crosstalk in Cellular Immunity

Ying He,¹Kangni Wu,¹Yongxian Hu,¹Lixia Sheng,¹Ruxiu Tie,¹Binsheng Wang,¹and He Huang¹

Academic Editor: Catherine Bollard

Received10 Jul 2013

Revised15 Jan 2014

Accepted29 Jan 2014

Published06 Mar 2014

Abstract

T cells have been recognized as effectors with immunomodulatory functions in cellular immunity. These abilities enable them to interact with other immune cells, thus having the potential for treatment of various immune-mediated diseases with adoptive cell therapy. So far, the interactions between T cell and other immune cells have not been well defined. Here we will discuss the interactivities among them and the perspective on T cells for their use in immunotherapy could be imagined. The understanding of the crosstalk among the immune cells in immunopathology might be beneficial for the clinical application of T cell.

1. Introduction

T cell accounts for a small group, which is less than 10% of the T cell pool in healthy human individuals [1]. Strong evidence demonstrates that T cell participates as part of both innate and adaptive immunity. On activation, these cells can expand markedly and display various effector functions in immune responses. For example, chemokines and inflammatory cytokines release, potent cytolytic activity against tumor or microbial pathogens, and immunologic memory generation. These characteristics may contribute to the cell-cell contact manner of T cell with other immune cells.

Empirical studies demonstrate that T cells recognize transformed cells, microbial or tumor-expressed antigens, and then develop the immune surveillance functions [2]. It is clear that T cells are able to respond to pathogen-associated molecular patterns of infection and autoimmunity. Virtually, their functions are not limited to antitumor or antiviral actions but also involved in modulating immune system homeostasis [3]. And this homeostasis may depend on the cross-reactivities between T cells and their neighbour immune cells [4]. Selective stimulation of T cells in vivo for antitumor therapy was accompanied by unexpected expansion of natural killer cells (NK cells) in a clinical trial [5]. It cannot be clearly distinguished whether the antitumor effect is produced by anyone of these two cells or there exists a synergy effect between them. The cell-cell interactions between T cell and other immune cells are largely unknown and therefore, it is hard to assess their roles for the example above.

In recent clinical studies, suppressive regulatory T cells (Tregs) have been infused into patients to control the activation of alloreactive T lymphocytes after allogeneic haematopoietic stem cell transplantation (AHSCT) [6, 7]. Adoptive transfer of different immune cell subsets for treating cancer and/or immune-mediated diseases is increasingly being tested in clinical trials. The challenge for this therapy is how to efficiently exert regulatory effects on the target cells. As described above, T cell plays an important role in immune response and thus has the potential for such immune-based therapies. Therefore this raises the question how the T cell communicates with other immune cells. Understanding their crosstalk may be beneficial for the development of immunotherapeutic strategies.

2. T Cell and T Cell

T lymphocytes express either or T cell receptor heterodimers. Previous works have revealed the similarities between T cell and the more populous T cell in some aspects, such as cytolysis [8] and secretion of multiple cytokines [9]. These properties of T cells permit them to regulate many types of immune response and cellular activities, including those of the predominant subsets- T cells. A variety of studies show that V2⁺ T cells act like professional antigen-presenting cells (APCs) to take up and present antigens (Ags) to human T cells [10, 11], as well as in some mouse T cells [12]. This capacity for Ag presentation by T cells is considered to be a cooperative way in immune defense. Furthermore, the isopentenyl pyrophosphate- (IPP-) activated V2⁺ T cells can promote proliferation and differentiation of naïve CD8⁺ T cells [8] and even enhance the interferon (IFN)- production from autologous colonic T cells [13]. However, all of these results are derived from in vitro experiments. Still, little is known about whether these cell-cell interactivities can be investigated under both ex vivo and in vivo conditions.

From a mouse model, T cell depletion by anti- T cell receptor (TCR) monoclonal antibody GL3 followed by concomitant elevated numbers of T cells was described [14]. Likewise, the CD8⁺ T cell-mediated liver damage in Listeria-infected TCR^−/− mice could be prevented by transferred with T cells, and this effect may depend upon the ability of T cells to reduce tumour necrosis factor (TNF)- secretion or expansion of CD8⁺ T cells [15]. Obviously, there is homeostatic competition between T cells and T cells in vivo, and the IL-15 production and trans-presentation by dendritic cells (DCs) may be one possible mechanism for this activity [16]. Nevertheless, we cannot conclude that T cells only have immunosuppressive effects on T cells in vivo. An interesting result shows that inactivation and/or depletion of V4⁺ T cells in the complete Freund’s adjuvant- (CFA-) treated mice lead(s) to significant decreased number of T cells as well as reduced TNF- and IFN- production [17]. These results provide the concept that the modulation effects of T cell on T lymphocyte are mysterious. There has been no explanation so far for such discrepancy.

By studying the lymphocytes, it has been found that CD8⁺ T cells potently inhibit T cells expansion and compete for essential cytokine stores when both of them are cotransferred into TCR^−/−/^−/− mice [4]. Similar results are seen in the CD4⁺CD25⁺ regulatory T cells, a subset of T cells, and they also have the capacity to suppress the expansion and functions of T cells [18]. However, when adoptive T cells (or CD4 T cells) were transferred into TCR^−/− mice, these cells positively restored interleukin-17⁺ (IL-17⁺) T cells generation, thereby implicating the supportive role of CD4⁺ T cells for IL-17⁺ T cells [19]. Taken together, these data demonstrate that the reciprocal effects between T cells and T cells are debatable. The possible reasons for the contradictory data may be the different functions of subsets of T cells, and the use of heterogeneous or homologous T lymphocytes also induces various immune responses.

3. T Cell and B Cell

In the T cell/B cell coculture experiments, the amounts of some immunoglobulins production increased remarkably [20, 21]. It is reported that T cells also can collaborate with B cells to support the germinal center formation [22, 23]. In addition, an in vivo finding showed that TCR^−/− mice still efficiently developed normal germinal center and produced immunoglobulins (Igs), which thus prompts the hypothesis that T cells might provide help for B cells [24]. In fact, not only the activation of immune responses but also the promotion of B cell maturation by T cell can be investigated in human [25]. It is clear that T cell is responsible, at least in part, for support of B cell functions. And recent investigations suggest that production of great amounts of cytokines from T cells may influence B cell responses in humoral immunity [26, 27].

Although most studies state the promotion of B cell activities by T cell, the limitation has been found under some circumstances. When mice received stimulation with ovalbumin (OVA) repeatedly, their splenic T cells can inhibit the primary IgE production [28]. These regulatory functions are speculated to be mediated by different T cells. For example, innate V1⁺ T cells, including V1V5⁺ subsets, can enhance IgE responses, whereas acquired V4⁺ T cells repress the T cell-dependent antigen-specific IgE responses [29]. Collectively, these findings suggest that T cells have complex immunomodulatory functions upon B lymphocytes similar to that on T cells and this phenomenon may be related to the subsets of T cells.

To understand whether the B cell can affect T cell, multiple studies are attempting to disclose their interactions. It is reported that allogeneic Epstein-Barr virus- (EBV-) transformed B cell lines augment the proliferation of V1⁺ T cells [30]. Further insights into the mechanism indicate that the isolated human peripheral blood B lymphocytes can induce proliferative response of V1⁺ T cells, and it may be attributed to the expression of B7 and CD39 molecules on the surface of activated B cells [31]. Because T cells undergo immune response independent of major histocompatibility complex (MHC) molecules, mutant EBV-transformed B cell lines lacking MHC molecules still can present the bacterial phosphoantigens (PAgs) to T cells for other T cells activation [32, 33]. Accordingly, rational combination of these two cell types for immunotherapies would be considerable.

4. T Cell and NK Cell

Similar to another lymphoid cell-NK cell, T cell exerts immune functions in the antibody-independent and non-MHC-dependent manners. Although the NK-cell-like functions of T cell are well characterized, the interactivity between T cell and NK cell remains enigmatic. Chapoval et al. showed that T cells were indispensable for regulation of NK-cell antitumor responses [34]. Afterwards they further identified that, in the TCR-^−/− mutant mice, early IFN- production seriously decreases in the listeriosis-infected group, and they also confirmed that NK cells were the critical producer of IFN- [35]. Maniar et al. have described a similar result that zoledronic acid-activated T cells can lead to enhancement of NK cell-mediated tumor cytotoxicity [36]. Recently, the DC-like cell-dependent NK cell cytokine production has been found to be controlled by T cells [37]. Thus these results manifest that lack of T cells may lead to impaired NK cells activation.

In turn, when stimulated by the antigens from M. tuberculosis, activated NK cells can improve T cells proliferation [38]. However, under in vivo condition, NK cells play a suppressive role in regulating T cells expansion in the absence of T cells [4]. Such phenomenon demonstrates that, different from the in vitro condition, the interplay between NK cells and T cells may lie on the competitive advantages of the cells under in vivo condition. Actually, NK cells or T cells use different mechanisms to mediate cytotoxicity functions, so the combination of them for immunotherapy would be considered. Understanding of their correlation may provide the concept for how to enhance the antitumor functions by immune cells.

5. T Cell and Monocyte/Macrophage

Monocytes play a role in immune defense and after travelling to tissues, they mature and differentiate into macrophage populations. At the sites of infection/inflammation, circulating T cells and monocytes are rapidly recruited to eliminate infected or transformed cells. Several investigations demonstrate that they do not function alone but affect each other. It is previously shown that microbe-responsive V9V2 T cells can induce monocytes differentiating into inflammatory DCs, which further results in production of inflammatory mediators and antigen-presenting functions of these differentiated monocytes [39]. In turn, some evidence suggests that M. tuberculosis-infected monocytes are potent in inducing T proliferation [40] and processing the M. tuberculosis for mycobacterial antigen-specific CD4⁺ and T cells [41]. After being incubated with M. tuberculosis Bacillus Calmette-Guérin (BCG), infected monocytes promote the cytotoxic activity of lymphocytes [42]. Additionally, the N-BP drug zoledronic acid-treated monocytes can effectively trigger activation of T cells [43]. But in atopic dermatitis (AD) patients, once contacted with activated monocytes, NK and T cells specifically undergo apoptosis associated with reduction of type 1 cytokine production [44]. It seems that different pathological states of monocytes may account for the fate of T cells.

In the case of macrophage, when incubated with Mycobacterium tuberculosis-derived products, macrophages release chemokines to efficiently recruit T cells as well as regulating the latter’s function [45]. As for T cell, different subsets may be responsible for their specific functions. In the mice infected with influenza A virus, V6V1⁺ T cells might contribute to the initial recruitment of macrophages whereas V4⁺ and V1⁺ T cells mediate elimination of macrophages [46]. For preventing the hyperinflammatory responses, T cells exert cytotoxic activity against activated macrophages [47]. Similarly, human or avian influenza virus-infected macrophages were killed by PAg-expanded T cells for virus clearance [48]. However, human peripheral V9V2 T cells have been shown to efficiently induce TNF- and IL-1 production of BCG-infected macrophages [49]. Obviously, different subtypes of T cells have their specific functions to regulate the activities of macrophages.

6. T Cell and DC

Unlike mouse T cells, human T cells distribute in the peripheral blood, spleen, lymph nodes, or the intraepithelial lymphocytes in intestine [50], but rare in human skin [51]. Various subsets of T cells scatter in a disparate anatomic location and assume distinct functions [52]. The 1⁺ T cell population abundant in lymphoid tissues markedly blocks the maturation and inhibits the function of DCs [53]. Interestingly, the V2⁺ T cells, which consist of most human peripheral blood T cells, seem to react in another way for DCs. When cocultured with V2⁺ T cells isolated from human blood samples, the maturation of immature DCs (iDCs) is shown to be potentiated [54], and the consistent phenomenon has been found in mice [55]. Furthermore, 92TCR-transduced T cells efficiently promote the maturation of DCs [56]. Apart from the induction of maturation of DCs, V9V2 T cells have been identified for their ability for restoring Brucella-infected DCs function [57]. It is also reported that T cells enhance DCs activation for the production of IL-12 [58]. The possible mechanism of T cell for the induction of DC activation may be due to recognition of the cell-surface molecules or inflammatory cytokines, such as CD1 [59], CD86 [60], CD40 [58], and IFN- [61]. However, a recent study found that the immunosenescence could be induced in the DCs by Treg cells [62]. Therefore, it is plausible that diverse effects of T cells on DCs may rely on different subsets.

It is investigated that DCs induce the cell cytokine production of freshly isolated V9V2 T cells [54], and they have the potent capacity to expand peripheral blood V2⁺ T cells [63] or support the development of V4⁺ T cells from the spleen [64]. Moreover, mycobacteria can induce V2 T cell antitumour responses indirectly via a specific subset of DCs [65]. These in vitro studies suggest that the modulation effect of DC on T cell is definite no matter what type of the T cell is. In tuberculosis patients, M. tuberculosis-infected DCs selectively induced expansion of phenotypically immature, central memory-type V9V2 T cells [66]. Even though, in the patients with multiple myeloma (MM), zoledronic acid-treated DCs are potent in activating autologous T cells [67], the above-mentioned findings, not only ex vivo but also in vivo study, are all suggestive of the promotion effects of DCs on T cells regardless of the latters’ subtype.

7. T Cell and Granulocyte

During inflammatory or infectious processes, granulocytes and T cells promptly accumulate at the site of inflamed tissues and eradicate the bacteria, virus, or transformed cells. It is established that T cells partially resemble the granulocytes in cytotoxic activities against pathogens. Understanding of their cross-reactivity in the immune response might pave the way for immunotherapies. Neutrophils constitute most of the granulocytes; hence the investigations on the activities of granulocytes are focused on this population. HMB-PP stimulated V9/V2 T cells have been reported to induce neutrophil survival and activation depending on the number of T cells [68]. Similarly, IPP or zoledronic acid-stimulated peripheral blood V9V2 T cells were observed to induce phagocytosis and migration of neutrophils [69], as well as granules release from activated granulocytes [70]. In addition, limbal epithelial T cells [71] and hepatic IL-17A⁺CD3⁺ TCR⁺ cells [72] have the capacity to regulate early infiltration or accumulation of neutrophils.

However, discrepant result reported that, in a mouse model of sepsis, there was a reverse association of the cell number between T cells and neutrophils, and T cells rapidly killed lipopolysaccharide- (LPS-) treated neutrophils [73]. At the presence of LPS—the major component of the membrane of Gram-negative bacteria—hypertonic saline leads to the increased elimination of inflammatory neutrophils by T cells [74]. These controversial results have not yet been well explained so far, and it seems to be attributed to the status of neutrophils. Unfortunately, the function of neutrophils on T cells has rarely been reported and the interaction between them should be further clarified.

8. T Cell and Mesenchymal Stromal Cell

Mesenchymal stem cells (MSCs) are a minor subset residing in several tissues, generally isolated from bone marrow. The ability of MSC to regulate other major immune cell populations has been demonstrated in numerous studies, but only a few studies elaborate the interplay between T cells and MSCs. The immunomodulatory activities of MSCs on T cells have been further investigated since it was confirmed that MSCs could inhibit the T lymphocytes proliferation either in mixed lymphocyte reactions or under the stimulation of polyclonal activators [75]. As recently reported, human MSCs inhibit the proliferation and immune responses of V9V2 T cells through prostaglandin E2 (PGE2) [76]. In addition, MSCs can suppress the expansion of V2⁺ T cells without affecting the functions of cytotoxicity or antigen processing/presentation to CD4⁺ T cells by V2⁺ T cells [77, 78]. The inhibitory role of MSC on T cell appears to be determined by the MSC-derived molecules [79]. It is interesting to note that when infection or organ injury develops, T cells increase the recruitment of MSCs to the site of infection [80]. Immunosuppressive effect of MSC is supposed to contribute to restoring tissue homeostasis whereas T cell exerts defending functions against pathogens and tumors. Therefore, the use of MSC or T cell in adoptive immunotherapy should carefully be taken into consideration for their interaction.

9. Concluding Remarks

A growing set of data has clearly identified that T cells play different roles in immune responses, thus providing a promising candidate for treatment of many diseases. More recently, T cells are making their way into clinical trials. In this review, the interactions between T cell and other immune cells have been discussed (Figure 1), and there is the prospect that T cells are potential for treating immune-mediated diseases. Unfortunately, current experimental data is almost derived from ex vivo studies or animal models, and there are extremely limited observations of the interaction between T cells and other immune cells in human body. This would impede the application of T cells for clinical therapeutics in the future. Therefore, more preclinical and clinical investigations of T cells are needed for making effective strategies to harness immune responses in various diseases.

By studying the effects of T cells on other immune cells, T cells reveal a dual role so that it is not definite whether they would display active or suppressive function in immune activities. That T cells are prone to be the positive or negative effectors may depend on their subtype or internal homeostasis. In this regard, strategies to regulate the interaction of these cells should be targeted on specific subsets as well as environmental factors. With regard to the modulation of other immune cells on T cell, most of them have the role of supporting the function of T cell except the inhibitive effects from MSC. Thus, the balance between T cells and their neighbour immune cells should be considered sufficiently in the adoptive cell therapies for treating cancer or immune-related diseases.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81230014, 81200338, 81170526, and 81270640) and the Natural Science Foundation of Zhejiang Province, China (Y2110152).

References

N. Williams, “T cells on the mucosal frontline,” Science, vol. 280, no. 5361, pp. 198–200, 1998.
View at: Publisher Site | Google Scholar
P. Vantourout and A. Hayday, “Six-of-the-best: unique contributions of gd T cells to immunology,” Nature Reviews Immunology, vol. 13, no. 2, pp. 88–100, 2013.
View at: Google Scholar
J. F. Bukowski, C. T. Morita, and M. B. Brenner, “Human γδ T cells recognize alkylamines derived from microbes, edible plants, and tea: implications for innate immunity,” Immunity, vol. 11, no. 1, pp. 57–65, 1999.
View at: Publisher Site | Google Scholar
J. D. French, C. L. Roark, W. K. Born, and R. L. O'Brien, “γδ T cell homeostasis is established in competition with αβ T cells and NK cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 41, pp. 14741–14746, 2005.
View at: Publisher Site | Google Scholar
V. Kunzmann, M. Smetak, B. Kimmel et al., “Tumor-promoting versus tumor-antagonizing roles of γδ T cells in cancer immunotherapy: results from a prospective phase I/II trial,” Journal of Immunotherapy, vol. 35, no. 2, pp. 205–213, 2012.
View at: Publisher Site | Google Scholar
C. G. Brunstein, J. S. Miller, Q. Cao et al., “Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics,” Blood, vol. 117, no. 3, pp. 1061–1070, 2011.
View at: Publisher Site | Google Scholar
M. Di Ianni, F. Falzetti, A. Carotti et al., “Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation,” Blood, vol. 117, no. 14, pp. 3921–3928, 2011.
View at: Publisher Site | Google Scholar
S. Bauer, V. Groh, J. Wu et al., “Activation of NK cells and T cells by NKG2D, a receptor for stress- inducible MICA,” Science, vol. 285, no. 5428, pp. 727–729, 1999.
View at: Publisher Site | Google Scholar
L. R. Sardinha, R. M. Elias, T. Mosca et al., “Contribution of NK, NK T, γδ T, and αβ T cells to the gamma interferon response required for liver protection against Trypanosoma cruzi,” Infection and Immunity, vol. 74, no. 4, pp. 2031–2042, 2006.
View at: Publisher Site | Google Scholar
M. Brandes, K. Willimann, and B. Moser, “Professional antigen-presentation function by human γδ cells,” Science, vol. 309, no. 5732, pp. 264–268, 2005.
View at: Publisher Site | Google Scholar
M. Brandes, K. Willimann, G. Bioley et al., “Cross-presenting human γδ T cells induce robust CD8⁺αβ T cell responses,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 7, pp. 2307–2312, 2009.
View at: Publisher Site | Google Scholar
L. Cheng, Y. Cui, H. Shao et al., “Mouse γδ T cells are capable of expressing MHC class II molecules, and of functioning as antigen-presenting cells,” Journal of Neuroimmunology, vol. 203, no. 1, pp. 3–11, 2008.
View at: Publisher Site | Google Scholar
N. E. McCarthy, Z. Bashir, A. Vossenkämper et al., “Proinflammatory Vδ2⁺T cells populate the human intestinal mucosa and enhance IFN-γ production by colonic αβ T cells,” The Journal of Immunology, vol. 191, no. 5, pp. 2752–2763, 2013.
View at: Google Scholar
S. H. Kaufmann, C. Blum, and S. Yamamoto, “Crosstalk between α/β T cells and γ/δ T cells in vivo: activation of α/β T-cell responses after γ/δ T-cell modulation with the monoclonal antibody GL3,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 20, pp. 9620–9624, 1993.
View at: Google Scholar
K. A. Rhodes, E. M. Andrew, D. J. Newton, D. Tramonti, and S. R. Carding, “A subset of IL-10-producing γδ T cells protect the liver from Listeria-elicited, CD8⁺ T cell-mediated injury,” European Journal of Immunology, vol. 38, no. 8, pp. 2274–2283, 2008.
View at: Publisher Site | Google Scholar
J.-S. Do and B. Min, “IL-15 produced and trans-presented by DCs underlies homeostatic competition between CD8 and γδ T cells in vivo,” Blood, vol. 113, no. 25, pp. 6361–6371, 2009.
View at: Publisher Site | Google Scholar
C. L. Roark, Y. F. Huang, N. Y. Jin et al., “A canonical Vγ4Vδ4+γδ T cell population with distinct stimulation requirements which promotes the Th17 response,” Immunologic Research, vol. 55, no. 1–3, pp. 217–230, 2013.
View at: Google Scholar
N. Gonçalves-Sousa, J. C. Ribot, A. DeBarros, D. V. Correia, Í. Caramalho, and B. Silva-Santos, “Inhibition of murine γδ lymphocyte expansion and effector function by regulatory αβ T cells is cell-contactdependent and sensitive to GITR modulation,” European Journal of Immunology, vol. 40, no. 1, pp. 61–70, 2010.
View at: Publisher Site | Google Scholar
J.-S. Do, A. Visperas, R. L. O'Brien, and B. Min, “CD4 T cells play important roles in maintaining IL-17-producing γδ T-cell subsets in naive animals,” Immunology and Cell Biology, vol. 90, no. 4, pp. 396–403, 2012.
View at: Publisher Site | Google Scholar
M. Felices, C. C. Yin, Y. Kosaka, J. Kang, and L. J. Berg, “Tec kinase Itk in γδT cells is pivotal for controlling IgE production in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 20, pp. 8308–8313, 2009.
View at: Publisher Site | Google Scholar
L. Wen, W. Pao, F. S. Wong et al., “Germinal center formation, immunoglobulin class switching, and autoantibody production driven by “non α/β” T cells,” The Journal of Experimental Medicine, vol. 183, no. 5, pp. 2271–2282, 1996.
View at: Google Scholar
B. Zheng, E. Marinova, J. Han, T.-H. Tan, and S. Han, “Cutting edge: γδ T cells provide help to B Cells with altered clonotypes and are capable of inducing Ig gene hypermutation,” The Journal of Immunology, vol. 171, no. 10, pp. 4979–4983, 2003.
View at: Google Scholar
L. Wen and A. C. Hayday, “γδ T-cell help in responses to pathogens and in the development of systemic autoimmunity,” Immunologic Research, vol. 16, no. 3, pp. 229–241, 1997.
View at: Google Scholar
L. Wen, W. Pao, F. S. Wong et al., “Germinal center formation, immunoglobulin class switching, and autoantibody production driven by “non α/β” T cells,” The Journal of Experimental Medicine, vol. 183, no. 5, pp. 2271–2282, 1996.
View at: Google Scholar
D. Vermijlen, P. Ellis, C. Langford et al., “Distinct cytokine-driven responses of activated blood γδ T cells: insights into unconventional T cell pleiotropy,” The Journal of Immunology, vol. 178, no. 7, pp. 4304–4314, 2007.
View at: Google Scholar
A. C. Hayday, “γδ cells: a right time and a right place for a conserved third way of protection,” Annual Review of Immunology, vol. 18, pp. 975–1026, 2000.
View at: Publisher Site | Google Scholar
S. R. Carding and P. J. Egan, “γδ T cells: functional plasticity and heterogeneity,” Nature Reviews Immunology, vol. 2, no. 5, pp. 336–345, 2002.
View at: Google Scholar
C. McMenamin, C. Pimm, M. McKersey, and P. G. Holt, “Regulation of IgE responses to inhaled antigen in mice by antigen-specific γδ T cells,” Science, vol. 265, no. 5180, pp. 1869–1871, 1994.
View at: Google Scholar
Y. Huang, N. Jin, C. L. Roark et al., “The influence of IgE-enhancing and IgE-suppressive γδ T cells changes with exposure to inhaled ovalbumin,” The Journal of Immunology, vol. 183, no. 2, pp. 849–855, 2009.
View at: Publisher Site | Google Scholar
G. Hacker, S. Kromer, M. Falk, K. Heeg, H. Wagner, and K. Pfeffer, “Vδ1⁺ subset of human γδ T cells responds to ligands expressed by EBV- infected Burkitt lymphoma cells and transformed B lymphocytes,” The Journal of Immunology, vol. 149, no. 12, pp. 3984–3989, 1992.
View at: Google Scholar
D. L. M. Orsini, M. van Gils, Y. M. C. Kooy et al., “Functional and molecular characterization of B cell-responsive Vδ1⁺γδ T cells,” European Journal of Immunology, vol. 24, no. 12, pp. 3199–3204, 1994.
View at: Publisher Site | Google Scholar
P. Fisch, M. Malkovsky, S. Kovats et al., “Recognition by human V(γ)9/V(δ)2 T cells of a GroEL homolog on Daudi Burkitt's lymphoma cells,” Science, vol. 250, no. 4985, pp. 1269–1273, 1990.
View at: Google Scholar
C. T. Morita, E. M. Beckman, J. F. Bukowski et al., “Direct presentation of nonpeptide prenyl pyrophosphate antigens to human γδ T cells,” Immunity, vol. 3, no. 4, pp. 495–507, 1995.
View at: Publisher Site | Google Scholar
A. I. Chapoval, J. A. Fuller, S. G. Kremlev, S. J. Kamdar, and R. Evans, “Combination chemotherapy and IL-15 administration induce permanent tumor regression in a mouse lung tumor model: NK and T cell-mediated effects antagonized by B cells,” The Journal of Immunology, vol. 161, no. 12, pp. 6977–6984, 1998.
View at: Google Scholar
C. H. Ladel, C. Blum, and S. H. E. Kaufmann, “Control of natural killer cell-mediated innate resistance against the intracellular pathogen Listeria monocytogenes by γ/δ T lymphocytes,” Infection and Immunity, vol. 64, no. 5, pp. 1744–1749, 1996.
View at: Google Scholar
A. Maniar, X. Zhang, W. Lin et al., “Human γδ T lymphocytes induce robust NK cell-mediated antitumor cytotoxicity through CD137 engagement,” Blood, vol. 116, no. 10, pp. 1726–1733, 2010.
View at: Publisher Site | Google Scholar
O. Nussbaumer, G. Gruenbacher, H. Gander, and M. Thurnher, “DC-like cell-dependent activation of human natural killer cells by the bisphosphonate zoledronic acid is regulated by γδ T lymphocytes,” Blood, vol. 118, no. 10, pp. 2743–2751, 2011.
View at: Publisher Site | Google Scholar
R. Zhang, X. Zheng, B. Li, H. Wei, and Z. Tian, “Human NK cells positively regulate γδ T cells in response to Mycobacterium tuberculosis,” The Journal of Immunology, vol. 176, no. 4, pp. 2610–2616, 2006.
View at: Google Scholar
M. Eberl, G. W. Roberts, S. Meuter, J. D. Williams, N. Topley, and B. Moser, “A rapid crosstalk of human γδ T cells and monocytes drives the acute inflammation in bacterial infections,” PLoS Pathogens, vol. 5, no. 2, Article ID e1000308, 2009.
View at: Publisher Site | Google Scholar
D. V. Havlir, J. J. Ellner, K. A. Chervenak, and W. H. Boom, “Selective expansion of human γΔ T cells by monocytes infected with live Mycobacterium tuberculosis,” Journal of Clinical Investigation, vol. 87, no. 2, pp. 729–733, 1991.
View at: Google Scholar
K. N. Balaji and W. H. Boom, “Processing of Mycobacterium tuberculosis bacilli by human monocytes for CD4⁺αβ and γδ T cells: role of particulate antigen,” Infection and Immunity, vol. 66, no. 1, pp. 98–106, 1998.
View at: Google Scholar
F. Miyagawa, Y. Tanaka, S. Yamashita, and N. Minato, “Essential requirement of antigen presentation by monocyte lineage cells for the activation of primary human γδ T cells by aminobisphosphonate antigen,” The Journal of Immunology, vol. 166, no. 9, pp. 5508–5514, 2001.
View at: Google Scholar
A. J. Roelofs, M. Jauhiainen, H. Mönkkönen, M. J. Rogers, J. Mönkkönen, and K. Thompson, “Peripheral blood monocytes are responsible for γδ T cell activation induced by zoledronic acid through accumulation of IPP/DMAPP,” British Journal of Haematology, vol. 144, no. 2, pp. 245–250, 2009.
View at: Publisher Site | Google Scholar
M. Katsuta, Y. Takigawa, M. Kimishima, M. Inaoka, R. Takahashi, and T. Shiohara, “NK cells and γδ⁺ T cells are phenotypically and functionally defective due to preferential apoptosis in patients with atopic dermatitis,” The Journal of Immunology, vol. 176, no. 12, pp. 7736–7744, 2006.
View at: Google Scholar
E. Ferrero, P. Biswas, K. Vettoretto et al., “Macrophages exposed to Mycobacterium tuberculosis release chemokines able to recruit selected leucocyte subpopulations: focus on γδ cells,” Immunology, vol. 108, no. 3, pp. 365–374, 2003.
View at: Publisher Site | Google Scholar
S. R. Carding, W. Allan, S. Kyes, A. Hayday, K. Bottomly, and P. C. Doherty, “Late dominance of the inflammatory process in murine influenza by γ/δ⁺ T cells,” The Journal of Experimental Medicine, vol. 172, no. 4, pp. 1225–1231, 1990.
View at: Google Scholar
D. Tramonti, K. Rhodes, N. Martin, J. E. Dalton, E. Andrew, and S. R. Carding, “γδT cell-mediated regulation of chemokine producing macrophages during Listeria monocytogenes infection-induced inflammation,” Journal of Pathology, vol. 216, no. 2, pp. 262–270, 2008.
View at: Publisher Site | Google Scholar
G. Qin, H. Mao, J. Zheng et al., “Phosphoantigen-expanded human γδ T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses,” Journal of Infectious Diseases, vol. 200, no. 6, pp. 858–865, 2009.
View at: Publisher Site | Google Scholar
C. T. Spencer, G. Abate, I. G. Sakala et al., “Granzyme A produced by γδ2T cells induces human macrophages to inhibit growth of an intracellular pathogen,” PLOS Pathogens, vol. 9, no. 1, Article ID e1003119, 2013.
View at: Google Scholar
R. P. Bucy, C.-L. H. Chen, J. Cihak, U. Losch, and M. D. Cooper, “Avian T cells expressing γδ receptors localize in the splenic sinusoids and the intestinal epithelium,” The Journal of Immunology, vol. 141, no. 7, pp. 2200–2205, 1988.
View at: Google Scholar
W. Holtmeier, M. Pfander, A. Hennemann, T. M. Zollner, R. Kaufmann, and W. F. Caspary, “The TCR δ repertoire in normal human skin is restricted and distinct from the TCR δ repertoire in the peripheral blood,” Journal of Investigative Dermatology, vol. 116, no. 2, pp. 275–280, 2001.
View at: Publisher Site | Google Scholar
M. Bonneville, R. L. O'Brien, and W. K. Born, “γδ T cell effector functions: a blend of innate programming and acquired plasticity,” Nature Reviews Immunology, vol. 10, no. 7, pp. 467–478, 2010.
View at: Publisher Site | Google Scholar
G. Peng, H. Y. Wang, W. Peng, Y. Kiniwa, K. H. Seo, and R.-F. Wang, “Tumor-infiltrating γδ T cells suppress T and dendritic cell function via mechanisms controlled by a unique toll-like receptor signaling pathway,” Immunity, vol. 27, no. 2, pp. 334–348, 2007.
View at: Publisher Site | Google Scholar
M. R. Dunne, L. Madrigal-Estebas, L. M. Tobin, and D. G. Doherty, “(E)-4-Hydroxy-3-methyl-but-2 enyl pyrophosphate-stimulated Vγ9Vδ2 T cells possess T helper type 1-promoting adjuvant activity for human monocyte-derived dendritic cells,” Cancer Immunology, Immunotherapy, vol. 59, no. 7, pp. 1109–1120, 2010.
View at: Publisher Site | Google Scholar
H. Fang, T. Welte, X. Zheng et al., “γδ T cells promote the maturation of dendritic cells during West Nile virus infection,” FEMS Immunology and Medical Microbiology, vol. 59, no. 1, pp. 71–80, 2010.
View at: Publisher Site | Google Scholar
V. Marcu-Malina, S. Heijhuurs, M. van Buuren et al., “Redirecting αβT cells against cancer cells by transfer of a broadly tumor-reactive γδT-cell receptor,” Blood, vol. 118, no. 1, pp. 50–59, 2011.
View at: Publisher Site | Google Scholar
M. Ni, D. Martire, E. Scotet, M. Bonneville, F. Sanchez, and V. Lafont, “Full restoration of Brucella-infected dendritic cell functionality through Vg9Vd2 T helper type 1 crosstalk,” PLoS ONE, vol. 7, no. 8, Article ID e43613, 2012.
View at: Google Scholar
S. I. Inoue, M. Niikura, S. Takeo et al., “Enhancement of dendritic cell activation via CD40 ligand-expressing gd T cells is responsible for protective immunity to Plasmodium parasites,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 30, pp. 12129–12134.
View at: Publisher Site | Google Scholar
D. S. Leslie, M. S. Vincent, F. M. Spada et al., “CD1-mediated γ/δ T cell maturation of dendritic cells,” The Journal of Experimental Medicine, vol. 196, no. 12, pp. 1575–1584, 2002.
View at: Publisher Site | Google Scholar
L. Conti, R. Casetti, M. Cardone et al., “Reciprocal activating interaction between dendritic cells and pamidronate-stimulated γδ T cells: role of CD86 and inflammatory cytokines,” The Journal of Immunology, vol. 174, no. 1, pp. 252–260, 2005.
View at: Google Scholar
M.-C. Devilder, S. Allain, C. Dousset, M. Bonneville, and E. Scotet, “Early triggering of exclusive IFN-γ responses of human Vγ9Vδ2 T cells by TLR-activated myeloid and plasmacytoid dendritic cells,” The Journal of Immunology, vol. 183, no. 6, pp. 3625–3633, 2009.
View at: Publisher Site | Google Scholar
J. Ye, C. L. Ma, E. C. Hsueh et al., “Tumor-derived gd regulatory T cells suppress innate and adaptive immunity through the induction of immunosenescence,” The Journal of Immunology, vol. 190, no. 5, pp. 2403–2414, 2013.
View at: Google Scholar
F. Cabillic, O. Toutirais, V. Lavoué et al., “Aminobisphosphonate-pretreated dendritic cells trigger successful Vγ9Vδ2 T cell amplification for immunotherapy in advanced cancer patients,” Cancer Immunology, Immunotherapy, vol. 59, no. 11, pp. 1611–1619, 2010.
View at: Publisher Site | Google Scholar
L. Cook, N. Miyahara, N. Jin et al., “Evidence that CD8⁺ dendritic cells enable the development of γδ T cells that modulate airway hyperresponsiveness,” The Journal of Immunology, vol. 181, no. 1, pp. 309–319, 2008.
View at: Google Scholar
D. W. Fowler, J. Copier, N. Wilson, A. G. Dalgleish, and M. D. Bodman-Smith, “Mycobacteria activate γδ T-cell anti-tumour responses via cytokines from type 1 myeloid dendritic cells: a mechanism of action for cancer immunotherapy,” Cancer Immunology, Immunotherapy, vol. 61, no. 4, pp. 535–547, 2012.
View at: Publisher Site | Google Scholar
S. Meraviglia, N. Caccamo, A. Salerno, G. Sireci, and F. Dieli, “Partial and ineffective activation of Vγ9Vδ2 T cells by Mycobacterium tuberculosis-infected dendritic cells,” The Journal of Immunology, vol. 185, no. 3, pp. 1770–1776, 2010.
View at: Publisher Site | Google Scholar
B. Castella, C. Riganti, F. Fiore et al., “Immune modulation by zoledronic acid in human myeloma: an advantageous cross-talk between Vγ9Vδ2 T cells, αβ CD8⁺ T cells, regulatory T cells, and dendritic cells,” The Journal of Immunology, vol. 187, no. 4, pp. 1578–1590, 2011.
View at: Publisher Site | Google Scholar
M. S. Davey, C.-Y. Lin, G. W. Roberts et al., “Human neutrophil clearance of bacterial pathogens triggers anti-microbial γδ T cell responses in early infection,” PLoS Pathogens, vol. 7, no. 5, Article ID e1002040, 2011.
View at: Publisher Site | Google Scholar
N. Caccamo, C. La Mendola, V. Orlando et al., “Differentiation, phenotype, and function of interleukin-17-producing human vγ9vδ2 T cells,” Blood, vol. 118, no. 1, pp. 129–138, 2011.
View at: Publisher Site | Google Scholar
C. Agrati, E. Cimini, A. Sacchi et al., “Activated Vγ9Vδ2 T cells trigger granulocyte functions via MCP-2 release,” The Journal of Immunology, vol. 182, no. 1, pp. 522–529, 2009.
View at: Google Scholar
Z. Li, A. R. Burns, R. E. Rumbaut, and C. W. Smith, “γδ T cells are necessary for platelet and neutrophil accumulation in limbal vessels and efficient epithelial repair after corneal abrasion,” American Journal of Pathology, vol. 171, no. 3, pp. 838–845, 2007.
View at: Publisher Site | Google Scholar
X. F. Wang, R. Sun, H. M. Wei, and Z. G. Tian, “High-mobility group box 1 (HMGB1)-toll-like receptor (TLR)4-interleukin (IL)-23-IL-17A axis in drug-induced damage-associated lethal hepatitis: interaction of gamma delta T cells with macrophages,” Hepatology, vol. 57, no. 1, pp. 373–384, 2013.
View at: Google Scholar
M. I. Hirsh, N. Hashiguchi, Y. Chen, L. Yip, and W. G. Junger, “Surface expression of HSP72 by LPS-stimulated neutrophils facilitates γδT cell-mediated killing,” European Journal of Immunology, vol. 36, no. 3, pp. 712–721, 2006.
View at: Publisher Site | Google Scholar
M. I. Hirsh, N. Hashiguchi, and W. G. Junger, “Hypertonic saline increases γδT cell-mediated killing of activated neutrophils,” Critical Care Medicine, vol. 36, no. 12, pp. 3220–3225, 2008.
View at: Publisher Site | Google Scholar
M. D. Nicola, C. Carlo-Stella, M. Magni et al., “Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli,” Blood, vol. 99, no. 10, pp. 3838–3843, 2002.
View at: Publisher Site | Google Scholar
L. Martinet, S. Fleury-Cappellesso, M. Gadelorge et al., “A regulatory cross-talk between Vγ9Vδ2 T lymphocytes and mesenchymal stem cells,” European Journal of Immunology, vol. 39, no. 3, pp. 752–762, 2009.
View at: Publisher Site | Google Scholar
I. Petrini, S. Pacini, M. Petrini, R. Fazzi, L. Trombi, and S. Galimberti, “Mesenchymal cells inhibit expansion but not cytotoxicity exerted by gamma-delta T cells,” European Journal of Clinical Investigation, vol. 39, no. 9, pp. 813–818, 2009.
View at: Publisher Site | Google Scholar
I. Prigione, F. Benvenuto, P. Bocca, L. Battistini, A. Uccelli, and V. Pistoia, “Reciprocal interactions between human mesenchymal stem cells and γδ T cells or invariant natural killer T cells,” Stem Cells, vol. 27, no. 3, pp. 693–702, 2009.
View at: Publisher Site | Google Scholar
M. Shi, Z.-W. Liu, and F.-S. Wang, “Immunomodulatory properties and therapeutic application of mesenchymal stem cells,” Clinical and Experimental Immunology, vol. 164, no. 1, pp. 1–8, 2011.
View at: Publisher Site | Google Scholar
J. Tschöp, A. Martignoni, H. S. Goetzman et al., “γδ T cells mitigate the organ injury and mortality of sepsis,” Journal of Leukocyte Biology, vol. 83, no. 3, pp. 581–588, 2008.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2014 Ying He et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

3054

Downloads

1183

Citations