Low-grade MALT-type lymphomas are malignancies of mucosal marginal-zone B cells
and preceded by reactive inflammatory lymphoid tissue. Experimental observations suggest that antigen
and CD40 Ligand act during cognate T/B cell interaction and are crucial for germinal center B-cell maturation
generating marginal-zone B cells. To investigate the mechanisms underlying the development of extranodal MALT-type lymphomas, the immunoglobulin receptor was sequenced and analyzed for antigen specificity using heterohybridoma technology.
Furthermore, CD40 ligand expression was evaluated by immunohistochemistry and by semiquantitative RT-PCR,
and ligand binding to the CD40 of tumor B cells was studied using the CD40 system. Hypermutations were found in low-grade
lymphomas throughout CDR1- CDR3 suggestive of positive selection through their antigen receptor.
Different VH families were used and more than 69% of tumor immunoglobulins bound different mucosal antigens.
CD40L expression was found in the tumor marginal zone in substantial amounts.
The in vitro proliferation response of all low-grade MALT-type lymphomas was dependent on
anti-CD40- mediated signals and cytokines. Our data provide evidence that autoantigen as well as the CD40L
expressed by activated nonneoplastic T cells may drive the evolution of low-grade MALT-type lymphomas either
directly or by paracrine mechanisms and that antigen may contribute to lymphoma pathogenesis.

A. Greiner

C. Knörr

Y. Qin

A. Schultz

A. Marx

R. A. Kroczek

H. K. Müller-Hermelink

CD40 Ligand and Autoantigen Are Involved in the Pathogenesis of Low-Grade B-Cell Lymphomas of Mucosa-Associated Lymphoid Tissue

The involvement of counteractive <mml:math id="E1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mtext>CD</mml:mtext><mml:msup><mml:mn>8</mml:mn><mml:mo>+</mml:mo></mml:msup></mml:mrow></mml:math> T-cell subsets during tumor-specific immune responses was analyzed in a syngeneic murine plasmacytoma model. <mml:math id="E2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mtext>CD</mml:mtext><mml:msup><mml:mn>8</mml:mn><mml:mo>+</mml:mo></mml:msup></mml:mrow></mml:math> Tc cells against the immunogenic IL-10-producing BALB/c plasmacytoma ADJ-PC-5 can be easily induced by immunization of BALB/c mice with X-irradiated ADJ-PC-5 tumor cells in vivo and in vitro. However, the failure of recipient mice to mount a protective Tc response against the tumor during early stages of a real or simulated tumor growth is not due to immunological ignorance,
but depends on the induction of tumor-specific tolerance, involving a population of tumorinduced <mml:math id="E3" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mtext>CD</mml:mtext><mml:msup><mml:mn>8</mml:mn><mml:mo>+</mml:mo></mml:msup></mml:mrow></mml:math> T cells that are able to inhibit the generation of tumor-specific Tc cells in a primary ADJ-PC-5-specific MLTC, using IFN-γ as a suppressive factor. Whereas most longterm cultivated CD8+ ADJ-PC-5-specific Tc lines produce type-1 cytokines on stimulation, at least two of them, which were derived from a primary MLTC, display a type-2 cytokine spectrum. Furthermore, the primary in vitro Tc response against ADJ-PC-5 cells shows characteristics of a Tc2 response. The Tc response is strictly depending on tumor-derived IL-10. <mml:math id="E4" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mtext>CD</mml:mtext><mml:msup><mml:mn>8</mml:mn><mml:mo>+</mml:mo></mml:msup></mml:mrow></mml:math> Tc cells that are induced in a primary MLTC do not produce IFN-γ, and the tumor-specific Tc response is enhanced by IL-4 but suppressed by IFN-γ or IL-12. In contrast, ADJ-PC- 5-specific <mml:math id="E5" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mtext>CD</mml:mtext><mml:msup><mml:mn>8</mml:mn><mml:mo>+</mml:mo></mml:msup></mml:mrow></mml:math> Tc cells from immunized mice are IFN-γ producing Tc1 cells. Since the primary
in vitro Tc response against the tumor is suppressed even by the smallest numbers of irradiated ADJ-PC-5-specific Tc1 cells via IFN-γ these Tc1 cells behave similar to the suppressive <mml:math id="E6" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mtext>CD</mml:mtext><mml:msup><mml:mn>8</mml:mn><mml:mo>+</mml:mo></mml:msup></mml:mrow></mml:math> T cells that are induced during early stages of ADJ-PC-5 tumorigenesis.

Christoph Specht

Hans-Gerd Pauels

Christian Becker

Eckehart Kölsch

Differential Activation of CD8+ Tumor-Specific Tc1 and Tc2 Cells by an IL-10-Producing Murine Plasmacytoma

Presented here is a cell-suspension model for positive selection using thymocytes from αβ-TCR
(H-2Db-restricted) transgenic mice specific to the lymphocytic choriomeningitis virus (LCMV)
on a nonselecting MHC background (H-2d or TAP-1 –/–), cocultured with freshly isolated adult
thymus stromal cells of the selecting MHC type. The thymic stromal cells alone induced positive
selection of functional CD4-CD8+ cells whose kinetics and efficiency were enhanced by
nominal peptide. Fibroblasts expressing the selecting MHC alone did not induce positive
selection; however, together with nonselecting stroma and nominal peptide, there was inefficient
positive. These results suggest multiple signaling in positive selection with selection events able
to occur on multiple-cell types. The ease with which this model can be manipulated should
greatly facilitate the resolution of the mechanisms of positive selection in normal and
pathological states.

Ann P. Chidgey

Hanspeter Pircher

H. Robson Macdonald

Richard L. Boyd

An Adult Thymic Stromal-Cell Suspension Model for in Vitro Positive Selection

Accessory-cell populations in the lymphoid tissues of fetal sheep were investigated following depletion ofB cells. An intraperitoneal injection of an anti-IgM antibody early in gestation resulted in a marked depletion of IgM+cells in lymphoid tissues. Immune and enzyme histochemical techniques were used to identify accessory-cellpopulations in the ileal Peyer&#39;s patch, spleen, and lymph nodes of B-cell-depleted fetal sheep. The rudimentaryfollicles in the ileal Peyer&#39;s patch showed strong enzyme reactivity for 5&#8242; nucleotidase, indicating the presenceof follicular dendritic cells (FDCs). Enzyme reactivities for FDCs in primary follicles of the spleen and lymph nodeswere absent, as were reactivities for metallophilic macrophages in the marginal zone of the spleen. MgATPasereactivity associated with dendritic-cell populations in the gut-associated lymphoid tissues was detected.A monoclonal antibody against complement receptor-2 (CD21) reacted with FDCs in the rudimentary follicles ofthe ileal Peyer&#39;s patch and immature FDCs in lymph nodes. The results suggest that the development of accessory-cellpopulations in B-cell compartments of peripheral but not central lymphoid tissues is dependent on the presence of B cells.

Charles Mcl. Press

John D. Reynolds

Susan J. McClure

Thor  Landsverk

Development of Accessory Cells in B-Cell Compartments Is Retarted in B-Cell-Depleted Fetal Sheep

Purified rat CD4+ T cells were activated in vitro, by the polyclonal mitogen Concanavalin A (Con A) or by
mixed lymphocyte reaction (MLR), in the presence or absence of the glucocorticoid dexamethasone (DEX).
They were then expanded in IL-2 and subsequently restimulated, this time in the absence of the hormone.
The results indicate that the exposure of the cells to DEX in the primary stimulation changed the cytokine synthesis
induced by the secondary stimulation. IL-4 production was increased by the pretreatment whereas synthesis of
IFN-γ was diminished. Addition of DEX in the second activation suppressed all cytokine
production. In brief, the transient presence of glucocorticoids in the culture induces a change in the pattern of
cytokine production but the continuous presence causes inhibition of cytokine synthesis. Further studies in which
IL-4 was used together with DEX showed that the cytokine potentiated the effect of the hormone.The data here presented suggest that glucocorticoids and the neuroendocrine system may be expected
to have long-term immunological effects as well as short-lived immunosuppressive ones. High concentration of
glucocorticoids suppress cytokine production but when steroids return to basal levels the immune response is
directed in a way that favors Th2-type reactions. Possible implications regarding the immune response to pathogens
and autoantigens are discussed.

Francisco Ramírez

Glucocorticoids Induce a TH2 Response In Vitro

Kalpit  A. Vora

Jeffrey V. Ravetch

Tim Manser

Insights into the Mechanisms of Antibody-Affinity Maturation and the Generation of the Memory B-Cell Compartment Using Genetically Altered Mice

Pregancy in the human presents an “immunological paradox,” because of the unexpected willingness of mothers to accept genetically disparate tissues. The fact that the fetus can develop unharmed for nine months shows that protective mechanisms must exist to permit its survival. The conditions that permit the genetically dissimilar human fetus to evade rejection by its mother's immune system have been the subject of intense interest for several decades. As the placental cells, which are in contact with maternal blood or tissue, are devoid of HLA class II antigens, interest has focused on the expression of HLA class molecules. Recent developments in the constitutive, transcriptional, and translational expression of HLA class I molecules on anatomically and morphologically different subpopulations of trophoblast cells will form the basis of this short review.

Heinz Hutter

Astrid Hammer

Gottfried Dohr

Joan S. Hunt

HLA Expression at the Maternal-Fetal Interface

Tingible body macrophages (TBM), long thought simply as scavengers of apoptotic lymphocytes, are located in the unique microenvironment of germinal centers in close proximity to antigen-retaining follicular dendritic cells (FDC). Observations that TBM endocytose FDC-iccosomal (immune-complex coated bodies) antigen suggested that TBM might present this antigen and help regulate the germinal center reaction. To test for antigen presentation, the ovalbumin (OVA)-specific TH hybridoma, 3DO-54.8, which produces IL-2 on receiving effective presentation of OVA, were used as responders to OVA-bearing TBM. Results showed that OVA-bearing TBM failed to induce IL-2 production. Furthermore, addition of TBM to IL- 2-inducing positive controls (B cells) not only failed to augment IL-2 production, but rather TBM significantly (55-90%) reduced B-cell induction of IL-2. We found that TBM were rich in prostaglandin by comparison with other nongerminal center lymph node macrophages and that addition of indomethacin to the cultures reversed the inhibitory effect of TBM. Depletion of TBM from enriched preparations, prior to addition to positive control cultures, also abrogated the inhibitory effect on IL-2 production. These data support the concept that TBM, within the unique microenvironment of germinal centers, may be specialized to downregulate the germinal center reaction.

John P. Smith

Gregory F. Burton

John G. Tew

Andras K. Szakal

Tinigible Body Macrophages in Regulation of Germinal Center Reactions

For several years, our group has been studying the in vivo role of adrenergic and cholinergic mechanisms in the immune-neuroendocrine dialogue in the rat model. The main results of these studies can be summarized as follows: (1) exogenous or endogenous catecholamines suppress PBL functions through alpha-2-receptor-mediated mechanisms, lymphocytes of the spleen are resistant to adrenergic in vivo stimulation, (2) direct or indirect cholinergic treatment leads to enhanced ex vivo functions of splenic and thymic lymphocytes leaving PBL unaffected, (3) cholinergic pathways play a critical role in the “talking back” of the immune system to the brain, (4) acetylcholine inhibits apoptosis of thymocytes possibly via direct effects on thymic epithelial cells, and may thereby influence T-cell maturation, (5) lymphocytes of the various immunological compartments were found to be equipped with the key enzymes for the synthesis of both acetylcholine and norepinephrine, and to secrete these neurotransmitters in culture supernatants

I. Rinner

P. Felsner

P. M. Liebmann

D. Hofer

A. Wölfler

A. Globerson

K. Schauenstein

Adrenergic/Cholinergic Immunomodulation in the Rat Model—In Vivo Veritas?

About this journal

Journal of Immunology Research provides a platform for scientists and clinicians working in different and diverse areas of immunology and therapy.

Journal profile

Meet the editorial board

Chief Editor, Professor Holland, has a background focusing on researching the development of conjunctival fibrosis and the characterisation of immune responses to potential C. trachomatis vaccine candidates.

Editor spotlight

Submit to Special Issue

We currently have a number of Special Issues open for submission. Special Issues highlight emerging areas of research within a field, or provide a venue for a deeper investigation into an existing research area.

Special Issues

Author guidelines

Editorial board

Databases and indexing

title

Journal of Immunology Research provides a platform for scientists and clinicians working in different and diverse areas of immunology and therapy.

description

https://images.hindawi.com/journals/jir/jir.banner.jpg

twitter:card

twitter:description

twitter:site

twitter:title

twitter:url

twitter:image

Journal of Immunology Research | Hindawi

Journal of Immunology Research

This Issue is now open for submissions.
Papers are published upon acceptance, regardless of the Special Issue publication date.

Call for papers

Richard Boyd

Konrad Schauenstein