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Clinical and Developmental Immunology
Volume 2013, Article ID 427696, 6 pages
http://dx.doi.org/10.1155/2013/427696
Review Article

Neonatal Natural Killer Cell Function: Relevance to Antiviral Immune Defense

1Department of Obstetrics/Gynecology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
2Division of Asthma, Allergy, and Rheumatology, Department of Pediatrics, Chang Gung Children’s Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

Received 17 June 2013; Revised 19 July 2013; Accepted 25 July 2013

Academic Editor: Mario Clerici

Copyright © 2013 Yen-Chang Lee and Syh-Jae Lin. 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.

Linked References

  1. M. A. Caligiuri, “Human natural killer cells,” Blood, vol. 112, no. 3, pp. 461–469, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. J. S. Orange and Z. K. Ballas, “Natural killer cells in human health and disease,” Clinical Immunology, vol. 118, no. 1, pp. 1–10, 2006. View at Publisher · View at Google Scholar · View at Scopus
  3. T. A. Fehniger, S. F. Cai, X. Cao et al., “Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAs,” Immunity, vol. 26, no. 6, pp. 798–811, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. A. Diefenbach, E. R. Jensen, A. M. Jamieson, and D. H. Raulet, “Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity,” Nature, vol. 413, no. 6852, pp. 165–171, 2001. View at Publisher · View at Google Scholar · View at Scopus
  5. D. Pende, C. Cantoni, P. Rivera et al., “Role of NKG2D in tumor cell lysis mediated by human NK cells: cooperation with natural cytotoxicity receptors and capability of recognizing tumors of nonepithelial origin,” European Journal of Immunology, vol. 31, pp. 1076–1086, 2001. View at Google Scholar
  6. A. Moretta, C. Bottino, M. C. Mingari, R. Biassoni, and L. Moretta, “What is a natural killer cell?” Nature Immunology, vol. 3, no. 1, pp. 6–8, 2002. View at Publisher · View at Google Scholar · View at Scopus
  7. L. L. Lanier, “NK cell recognition,” Annual Review of Immunology, vol. 23, pp. 225–274, 2005. View at Google Scholar
  8. M. A. Cooper, T. A. Fehniger, S. C. Turner et al., “Human natural killer cells: a unique innate immunoregulatory role for the CD56bright subset,” Blood, vol. 97, no. 10, pp. 3146–3151, 2001. View at Publisher · View at Google Scholar · View at Scopus
  9. Q. H. Nguyen, R. L. Roberts, B. J. Ank, S.-J. Lin, E. K. Thomas, and E. R. Stiehm, “Interleukin (IL)-15 enhances antibody-dependent cellular cytotoxicity and natural killer activity in neonatal cells,” Cellular Immunology, vol. 185, no. 2, pp. 83–92, 1998. View at Publisher · View at Google Scholar · View at Scopus
  10. S.-J. Lin and M.-L. Kuo, “Cytotoxic function of umbilical cord blood natural killer cells: relevance to adoptive immunotherapy,” Pediatric Hematology and Oncology, vol. 28, no. 8, pp. 640–646, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. Y. Zhang, G. Cheng, Z. W. Xu et al., “Down regulation of TRAIL and FasL on NK cells by Cyclosporin A in renal transplantation patients,” Immunology Letters, vol. 152, pp. 1–7, 2013. View at Google Scholar
  12. B. Perussia, Y. Chen, and M. J. Loza, “Peripheral NK cell phenotypes: multiple changing of faces of an adapting, developing cell,” Molecular Immunology, vol. 42, no. 4, pp. 385–395, 2005. View at Publisher · View at Google Scholar · View at Scopus
  13. M. A. Degli-Esposti and M. J. Smyth, “Close encounters of different kinds: dendritic cells and NK cells take centre stage,” Nature Reviews Immunology, vol. 5, no. 2, pp. 112–124, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. S. H. Robbins, G. Bessou, A. Cornillon et al., “Natural killer cells promote early CD8 T cell responses against cytomegalovirus,” PLoS Pathogens, vol. 3, no. 8, article e123, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. D. Rudnicka, A. Oszmiana, D. K. Finch et al., “Rituximab causes a polarization of B cells that augments its therapeutic function in NK-cell-mediated antibody-dependent cellular cytotoxicity,” Blood, vol. 121, pp. 4694–4702, 2013. View at Google Scholar
  16. M. C. López, B. E. Palmer, and D. A. Lawrence, “Phenotypic differences between cord blood and adult peripheral blood,” Cytometry Part B, vol. 76, no. 1, pp. 37–46, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. T. W. Chin, B. J. Ank, and D. Murakami, “Cytotoxic studies in human newborns: lessened allogeneic cell-induced (augmented) cytotoxicity but strong lymphokine-activated cytotoxicity of cord mononuclear cells,” Cellular Immunology, vol. 103, no. 2, pp. 241–251, 1986. View at Google Scholar · View at Scopus
  18. J. D. Peoples, S. Cheung, M. Nesin et al., “Neonatal cord blood subsets and cytokine response to bacterial antigens,” American Journal of Perinatology, vol. 26, no. 9, pp. 647–657, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. J. Gaddy and H. E. Broxmeyer, “Cord blood CD16+56 cells with low lytic activity are possible precursors of mature natural killer cells,” Cellular Immunology, vol. 180, no. 2, pp. 132–142, 1997. View at Publisher · View at Google Scholar · View at Scopus
  20. J.-H. Dalle, J. Menezes, É. Wagner et al., “Characterization of cord blood natural killer cells: implications for transplantation and neonatal infections,” Pediatric Research, vol. 57, no. 5, pp. 649–655, 2005. View at Publisher · View at Google Scholar · View at Scopus
  21. H. Tanaka, S. Kai, M. Yamaguchi et al., “Analysis of natural killer (NK) cell activity and adhesion molecules on NK cells from umbilical cord blood,” European Journal of Haematology, vol. 71, no. 1, pp. 29–38, 2003. View at Publisher · View at Google Scholar · View at Scopus
  22. S. Lopez-Vergès, J. M. Milush, S. Pandey et al., “CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset,” Blood, vol. 116, no. 19, pp. 3865–3874, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. M. Luevano, M. Daryouzeh, R. Alnabhan et al., “The unique profile of cord blood natural killer cells balances incomplete maturation and effective killing function upon activation,” Human Immunology, vol. 73, no. 3, pp. 248–257, 2012. View at Publisher · View at Google Scholar · View at Scopus
  24. S.-J. Lin and M.-L. Kuo, “Effect of cyclosporin A on interleukin-15-activated umbilical cord blood natural killer cell function,” Cytotherapy, vol. 10, no. 4, pp. 397–405, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. S.-J. Lin and D.-C. Yan, “ICAM-1 (CD54) expression on T lymphocytes and natural killer cells from umbilical cord blood: regulation with interleukin-12 and interleukin-15,” Cytokines, Cellular and Molecular Therapy, vol. 6, no. 4, pp. 161–164, 2000. View at Google Scholar · View at Scopus
  26. S.-J. Lin, P.-J. Cheng, T.-Y. Lin, P.-T. Lee, H.-S. Hsiao, and M.-L. Kuo, “Effect of influenza a infection on umbilical cord blood natural killer function regulation with interleukin-15,” Journal of Infectious Diseases, vol. 205, no. 5, pp. 745–756, 2012. View at Publisher · View at Google Scholar · View at Scopus
  27. Y. Sundström, C. Nilsson, G. Lilja, K. Kärre, M. Troye-Blomberg, and L. Berg, “The expression of human natural killer cell receptors in early life,” Scandinavian Journal of Immunology, vol. 66, no. 2-3, pp. 335–344, 2007. View at Publisher · View at Google Scholar · View at Scopus
  28. Y. Wang, H. Xu, X. Zheng, H. Wei, R. Sun, and Z. Tian, “High expression of NKG2A/CD94 and low expression of granzyme B are associated with reduced cord blood NK cell activity,” Cellular & Molecular Immunology, vol. 4, no. 5, pp. 377–382, 2007. View at Google Scholar · View at Scopus
  29. P. M. Sondel and K. L. Alderson, “Clinical cancer therapy by NK cells via antibody-dependent cell-mediated cytotoxicity,” Journal of Biomedicine and Biotechnology, vol. 2011, Article ID 379123, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. S.-J. Lin, M.-H. Yang, H.-C. Chao, M.-L. Kou, and J.-L. Huang, “Effect of interleukin-15 and Flt3-ligand on natural killer cell expansion and activation: umbilical cord vs. adult peripheral blood mononuclear cell,” Pediatric Allergy and Immunology, vol. 11, no. 3, pp. 168–174, 2000. View at Google Scholar · View at Scopus
  31. S. S. Choi, V. S. Chhabra, Q. H. Nguyen, B. J. Ank, E. R. Stiehm, and R. L. Roberts, “Interleukin-15 enhances cytotoxicity, receptor expression, and expansion of neonatal natural killer cells in long-term culture,” Clinical and Diagnostic Laboratory Immunology, vol. 11, no. 5, pp. 879–888, 2004. View at Publisher · View at Google Scholar · View at Scopus
  32. I. Engelmann, U. Moeller, A. Santamaria, P. G. Kremsner, and A. J. F. Luty, “Differing activation status and immune effector molecule expression profiles of neonatal and maternal lymphocytes in an African population,” Immunology, vol. 119, no. 4, pp. 515–521, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. D. Xing, A. G. Ramsay, J. G. Gribben et al., “Cord blood natural killer cells exhibit impaired lytic immunological synapse formation that is reversed with il-2 exvivo expansion,” Journal of Immunotherapy, vol. 33, no. 7, pp. 684–696, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. S.-J. Lin, P.-J. Cheng, Y.-J. Huang, and M.-L. Kuo, “Evaluation of cytotoxic function and apoptosis in interleukin (IL)-12/IL-15-treated umbilical cord or adult peripheral blood natural killer cells by a propidium-iodide based flow cytometry,” Pediatric Allergy and Immunology, vol. 15, no. 1, pp. 79–85, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Krampera, L. Tavecchia, F. Benedetti, G. Nadali, and G. Pizzolo, “Intracellular cytokine profile of cord blood T-, and NK- cells and monocytes,” Haematologica, vol. 85, no. 7, pp. 675–679, 2000. View at Google Scholar · View at Scopus
  36. A. S. Lau, M. Sigaroudinia, M. C. Yeung, and S. Kohl, “Interleukin-12 induces interferon-γ expression and natural killer cytotoxicity in cord blood mononuclear cells,” Pediatric Research, vol. 39, no. 1, pp. 150–155, 1996. View at Google Scholar · View at Scopus
  37. A. Nomura, H. Takada, C.-H. Jin, T. Tanaka, S. Ohga, and T. Hara, “Functional analyses of cord blood natural killer cells and T cellsa distinctive interleukin-18 response,” Experimental Hematology, vol. 29, no. 10, pp. 1169–1176, 2001. View at Publisher · View at Google Scholar · View at Scopus
  38. J. M. Palmer, K. Rajasekaran, M. S. Thakar, and S. Malarkannan, “Clinical relevance of natural killer cells following hematopoietic stem cell transplantation,” Journal of Cancer, vol. 4, pp. 25–35, 2013. View at Google Scholar
  39. C. H. Tay, E. Szomolanyi-Tsuda, and R. M. Welsh, “Control of infections by NK cells,” Current Topics in Microbiology and Immunology, vol. 230, pp. 193–220, 1998. View at Google Scholar · View at Scopus
  40. C. A. Biron, K. B. Nguyen, G. C. Pien, L. P. Cousens, and T. P. Salazar-Mather, “Natural killer cells in antiviral defense: function and regulation by innate cytokines,” Annual Review of Immunology, vol. 17, pp. 189–220, 1999. View at Publisher · View at Google Scholar · View at Scopus
  41. A. Poli, T. Michel, M. Thérésine, E. Andrès, F. Hentges, and J. Zimmer, “CD56bright natural killer (NK) cells: an important NK cell subset,” Immunology, vol. 126, no. 4, pp. 458–465, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. T. A. Fehniger, M. A. Cooper, G. J. Nuovo et al., “CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity,” Blood, vol. 101, no. 8, pp. 3052–3057, 2003. View at Publisher · View at Google Scholar · View at Scopus
  43. A. Moretta, M. Vitale, C. Bottino et al., “P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities,” Journal of Experimental Medicine, vol. 178, no. 2, pp. 597–604, 1993. View at Google Scholar · View at Scopus
  44. A. Moretta, C. Bottino, M. Vitale et al., “Receptors for HLA class-I molecules in human natural killer cells,” Annual Review of Immunology, vol. 14, pp. 619–648, 1996. View at Publisher · View at Google Scholar · View at Scopus
  45. S. Sivori, D. Pende, C. Bottino et al., “NKp46 is the major triggering receptor involved in the natural cytotoxicity of fresh or cultured human NK cells. Correlation between surface density of NKp46 and natural cytotoxicity against autologous, allogeneic or xenogeneic target cells,” European Journal of Immunology, vol. 29, pp. 1656–1666, 1999. View at Google Scholar
  46. O. Mandelboim, N. Lieberman, M. Lev et al., “Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells,” Nature, vol. 409, no. 6823, pp. 1055–1060, 2001. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Jinushi, T. Takehara, T. Tatsumi et al., “Negative regulation of NK cell activities by inhibitory receptor CD94/NKG2A leads to altered NK cell-induced modulation of dendritic cell functions in chronic hepatitis C virus infection,” Journal of Immunology, vol. 173, no. 10, pp. 6072–6081, 2004. View at Google Scholar · View at Scopus
  48. G. Ferlazzo, M. L. Tsang, L. Moretta, G. Melioli, R. M. Steinman, and C. Münz, “Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells,” Journal of Experimental Medicine, vol. 195, no. 3, pp. 343–351, 2002. View at Publisher · View at Google Scholar · View at Scopus
  49. L. Zitvogel, “Dendritic and natural killer cells cooperate in the control/switch of innate immunity,” Journal of Experimental Medicine, vol. 195, no. 3, pp. F9–F14, 2002. View at Google Scholar · View at Scopus
  50. L. G. Guidotti and F. V. Chisari, “Noncytolytic control of viral infections by the innate and adaptive immune response,” Annual Review of Immunology, vol. 19, pp. 65–91, 2001. View at Publisher · View at Google Scholar · View at Scopus
  51. T. P. Salazar-Mather, C. A. Lewis, and C. A. Biron, “Type I interferons regulate inflammatory cell trafficking and macrophage inflammatory protein 1α delivery to the liver,” Journal of Clinical Investigation, vol. 110, no. 3, pp. 321–330, 2002. View at Publisher · View at Google Scholar · View at Scopus
  52. M. A. Pak-Wittel, L. Yang, D. K. Sojka, J. G. Rivenbark, and W. M. Yokoyama, “Interferon-γ mediates chemokine-dependent recruitment of natural killer cells during viral infection,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, pp. E50–E59, 2013. View at Google Scholar
  53. J. S. Orange, “Human natural killer cell deficiencies and susceptibility to infection,” Microbes and Infection, vol. 4, no. 15, pp. 1545–1558, 2002. View at Publisher · View at Google Scholar · View at Scopus
  54. G. Fleisher, S. Starr, and N. Koven, “A non-X-linked syndrome with susceptibility to severe Epstein-Barr virus infections,” Journal of Pediatrics, vol. 100, no. 5, pp. 727–730, 1982. View at Google Scholar · View at Scopus
  55. S. Kim, J. B. Sunwoo, L. Yang et al., “HLA alleles determine differences in human natural killer cell responsiveness and potency,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 8, pp. 3053–3058, 2008. View at Publisher · View at Google Scholar · View at Scopus
  56. S. Cooley, F. Xiao, M. Pitt et al., “A subpopulation of human peripheral blood NK cells that lacks inhibitory receptors for self-MHC is developmentally immature,” Blood, vol. 110, no. 2, pp. 578–586, 2007. View at Publisher · View at Google Scholar · View at Scopus
  57. S. Kim, J. Poursine-Laurent, S. M. Truscott et al., “Licensing of natural killer cells by host major histocompatibility complex class I molecules,” Nature, vol. 436, no. 7051, pp. 709–713, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. K. Schönberg, J. C. Fischer, G. Kögler, and M. Uhrberg, “Neonatal NK-cell repertoires are functionally, but not structurally, biased toward recognition of self HLA class I,” Blood, vol. 117, no. 19, pp. 5152–5156, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. M. Gumá, A. Angulo, C. Vilches, N. Gómez-Lozano, N. Malats, and M. López-Botet, “Imprint of human cytomegalovirus infection on the NK cell receptor repertoire,” Blood, vol. 104, no. 12, pp. 3664–3671, 2004. View at Publisher · View at Google Scholar · View at Scopus
  60. H. N. Charoudeh, G. Terszowski, K. Czaja, A. Gonzalez, K. Schmitter, and M. Stern, “Modulation of the natural killer cell KIR repertoire by cytomegalovirus infection,” European Journal of Immunology, vol. 43, pp. 480–487, 2013. View at Google Scholar
  61. A. Monsiváis-Urenda, D. Noyola-Cherpitel, A. Hernández-Salinas et al., “Influence of human cytomegalovirus infection on the NK cell receptor repertoire in children,” European Journal of Immunology, vol. 40, pp. 1418–1427, 2010. View at Google Scholar
  62. C. Tomescu, S. Abdulhaqq, and L. J. Montaner, “Evidence for the innate immune response as a correlate of protection in human immunodeficiency virus (HIV)-1 highly exposed seronegative subjects (HESN),” Clinical and Experimental Immunology, vol. 164, no. 2, pp. 158–169, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. S.-J. Lin, R. L. Roberts, B. J. Ank, Q. H. Nguyen, E. K. Thomas, and E. R. Stiehm, “Effect of interleukin (IL)-12 and IL-15 on activated natural killer (ANK) and antibody-dependent cellular cytotoxicity (ADCC) in HIV infection,” Journal of Clinical Immunology, vol. 18, no. 5, pp. 335–345, 1998. View at Publisher · View at Google Scholar · View at Scopus
  64. S.-J. Lin, R. L. Roberts, B. J. Ank, Q. H. Nguyen, E. K. Thomas, and E. R. Stiehm, “Human immunodeficiency virus (HIV) type-1 GP120-specific cell-mediated cytotoxicity (CMC) and natural killer (NK) activity in HIV-infected (HIV+) subjects: enhancement with interleukin-2(IL-2), IL-12, and IL-15,” Clinical Immunology and Immunopathology, vol. 82, no. 2, pp. 163–173, 1997. View at Publisher · View at Google Scholar · View at Scopus
  65. V. Naranbhai, M. Altfeld, S. S. Karim, T. Ndung'u, Q. A. Karim, and W. H. Carr, “Changes in Natural Killer cell activation and function during primary HIV-1 Infection,” PLoS ONE, vol. 8, Article ID e53251, 2013. View at Google Scholar
  66. F. R. Guerini and M. Clerici, “NK cells in human disease: an evolving story,” Clinical Immunology, vol. 143, no. 3, pp. 203–206, 2012. View at Publisher · View at Google Scholar · View at Scopus
  67. W. M. Ballan, B.-A. N. Vu, B. R. Long et al., “Natural killer cells in perinatally HIV-1-infected children exhibit less degranulation compared to HIV-1-exposed uninfected children and their expression of KIR2DL3, NKG2C, and NKp46 correlates with disease severity,” Journal of Immunology, vol. 179, no. 5, pp. 3362–3370, 2007. View at Google Scholar · View at Scopus
  68. J. Zaunders and D. van Bockel, “Innate and adaptive immunity in long-term non-progression in HIV Disease,” Frontiers in Immunology, vol. 4, article 95, 2013. View at Google Scholar
  69. A. Soria, F. R. Guerini, A. Bandera et al., “KIR-HLA genotypes in HIV-infected patients lacking immunological recovery despite effective antiretroviral therapy,” PLoS ONE, vol. 6, no. 11, Article ID e27349, 2011. View at Publisher · View at Google Scholar · View at Scopus
  70. S. Kottilil, K. Shin, M. Planta et al., “Expression of chemokine and inhibitory receptors on natural killer cells: effect of immune activation and HIV viremia,” Journal of Infectious Diseases, vol. 189, no. 7, pp. 1193–1198, 2004. View at Publisher · View at Google Scholar · View at Scopus
  71. A. Oliva, A. L. Kinter, M. Vaccarezza et al., “Natural killer cells from human immunodeficiency virus (HIV)-infected individuals are an important source of CC-chemokines and suppress HIV-1 entry and replication in vitro,” Journal of Clinical Investigation, vol. 102, no. 1, pp. 223–231, 1998. View at Google Scholar · View at Scopus
  72. H. B. Bernstein, A. L. Kinter, R. Jackson, and A. S. Fauci, “Neonatal natural killer cells produce chemokines and suppress HIV replication in vitro,” AIDS Research and Human Retroviruses, vol. 20, no. 11, pp. 1189–1195, 2004. View at Publisher · View at Google Scholar · View at Scopus
  73. A. Jacobson, F. Bell, N. Lejarcegui, C. Mitchell, L. Frenkel, and H. Horton, “Healthy neonates possess a CD56-negative NK cell population with reduced anti-viral activity,” PLoS ONE, vol. 8, Article ID e67700, 2013. View at Google Scholar
  74. M. L. Heltzer, S. E. Coffin, K. Maurer et al., “Immune dysregulation in severe influenza,” Journal of Leukocyte Biology, vol. 85, no. 6, pp. 1036–1043, 2009. View at Publisher · View at Google Scholar · View at Scopus
  75. L. Denney, C. Aitken, C. K.-F. Li et al., “Reduction of natural killer but not effector CD8 T lymphoyctes in three consecutive cases of severe/lethal H1N1/09 influenza a virus infection,” PLoS ONE, vol. 5, no. 5, Article ID e10675, 2010. View at Publisher · View at Google Scholar · View at Scopus
  76. H. Mao, W. Tu, G. Qin et al., “Influenza virus directly infects human natural killer cells and induces cell apoptosis,” Journal of Virology, vol. 83, no. 18, pp. 9215–9222, 2009. View at Publisher · View at Google Scholar · View at Scopus
  77. H. S. Izurieta, W. W. Thompson, P. Kramarz et al., “Influenza and the rates of hospitalization for respiratory disease among infants and young children,” The New England Journal of Medicine, vol. 342, no. 4, pp. 232–239, 2000. View at Publisher · View at Google Scholar · View at Scopus
  78. S. E. Coffin, T. E. Zaoutis, A. B. W. Rosenquist et al., “Incidence, complications, and risk factors for prolonged stay in children hospitalized with community-acquired influenza,” Pediatrics, vol. 119, no. 4, pp. 740–748, 2007. View at Publisher · View at Google Scholar · View at Scopus
  79. K. H. Grabstein, J. Eisenman, K. Shanebeck et al., “Cloning of a T cell growth factor that interacts with the β chain of the interleukin-2 receptor,” Science, vol. 264, no. 5161, pp. 965–968, 1994. View at Google Scholar · View at Scopus
  80. W. E. Carson, T. A. Fehniger, S. Haldar et al., “A potential role for interleukin-15 in the regulation of human natural killer cell survival,” Journal of Clinical Investigation, vol. 99, no. 5, pp. 937–943, 1997. View at Google Scholar · View at Scopus
  81. T. Ranson, C. A. J. Vosshenrich, E. Corcuff, O. Richard, W. Müller, and J. P. Di Santo, “IL-15 is an essential mediator of peripheral NK-cell homeostasis,” Blood, vol. 101, no. 12, pp. 4887–4893, 2003. View at Google Scholar · View at Scopus
  82. J.-X. Lin, T.-S. Migone, M. Tsang et al., “The role of shared receptor motifs and common stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15,” Immunity, vol. 2, no. 4, pp. 331–339, 1995. View at Google Scholar · View at Scopus
  83. D. De Totero, R. Meazza, M. Capaia et al., “The opposite effects of IL-15 and IL-21 on CLL B cells correlate with differential activation of the JAK/STAT and ERK1/2 pathways,” Blood, vol. 111, no. 2, pp. 517–524, 2008. View at Publisher · View at Google Scholar · View at Scopus
  84. J. X. Qian, S. M. Lee, Y. Suen, E. Knoppel, C. Van De Ven, and M. S. Cairo, “Decreased interleukin-15 from activated cord versus adult peripheral blood mononuclear cells and the effect of interleukin-15 in upregulating antitumor immune activity and cytokine production in cord blood,” Blood, vol. 90, no. 8, pp. 3106–3117, 1997. View at Google Scholar · View at Scopus
  85. N. L. Alves, B. Hooibrink, F. A. Arosa, and R. A. W. Van Lier, “IL-15 induces antigen-independent expansion and differentiation of human naive CD8+ T cells in vitro,” Blood, vol. 102, no. 7, pp. 2541–2546, 2003. View at Publisher · View at Google Scholar · View at Scopus
  86. Y. Li, W. Zhi, P. Wareski, and N.-P. Weng, “IL-15 activates telomerase and minimizes telomere loss and may preserve the replicative life span of memory CD8+ T cells in vitro,” Journal of Immunology, vol. 174, no. 7, pp. 4019–4024, 2005. View at Google Scholar · View at Scopus
  87. N. Gill, K. L. Rosenthal, and A. A. Ashkar, “NK and NKT cell-independent contribution of interleukin-15 to innate protection against mucosal viral infection,” Journal of Virology, vol. 79, no. 7, pp. 4470–4478, 2005. View at Publisher · View at Google Scholar · View at Scopus
  88. Y. Kagimoto, H. Yamada, T. Ishikawa et al., “A regulatory role of interleukin 15 in wound healing and mucosal infection in mice,” Journal of Leukocyte Biology, vol. 83, no. 1, pp. 165–172, 2008. View at Publisher · View at Google Scholar · View at Scopus
  89. Y. M. Mueller, P. M. Bojczuk, E. S. Halstead et al., “IL-15 enhances survival and function of HIV-specific CD8+ T cells,” Blood, vol. 101, no. 3, pp. 1024–1029, 2003. View at Publisher · View at Google Scholar · View at Scopus
  90. G. D'Ettorre, G. Forcina, M. Lichtner et al., “Interleukin-15 in HIV infection: immunological and virological interactions in antiretroviral-naive and -treated patients,” AIDS, vol. 16, no. 2, pp. 181–188, 2002. View at Publisher · View at Google Scholar · View at Scopus