Role of IL-15 in immune-mediated and infectious diseases

Cytokine and Growth Factor Reviews

Volumn 22, Issue 1, 2011, Pages 19-33

  Di Sabatino, Antonio ^a   Calarota, Sandra A ^a   Vidali, Francesca ^a   MacDonald, Thomas T ^b   Corazza, Gino R ^a  

^a UNIVERSITY OF PAVIA   (Italy)

^b QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Autoimmune diseases; IL 15; Immune system; Immune therapeutic tool; Infectious diseases

Indexed keywords

4 [N [1 (2 CYANO 1 OXOETHYL) 4 METHYL 3 PIPERIDINYL] N METHYLAMINO]PYRROLO[2,3 D]PYRIMIDINE; AMG 714; IMMUNOGLOBULIN A; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M; INFLIXIMAB; INTERLEUKIN 12; INTERLEUKIN 15; MONOCYTE CHEMOTACTIC PROTEIN 1;

ADAPTIVE IMMUNITY; ANTIGEN PRESENTING CELL; AUTOIMMUNE DISEASE; AUTOIMMUNITY; B LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELIAC DISEASE; CELL DIFFERENTIATION; CELL EXPANSION; CELL MATURATION; CROHN DISEASE; CYTOKINE PRODUCTION; CYTOTOXICITY; DRUG EFFICACY; DRUG POTENCY; DRUG SAFETY; ENTERITIS; ENVIRONMENTAL EXPOSURE; GENE OVEREXPRESSION; GENETIC SUSCEPTIBILITY; HEPATITIS B; HERPES SIMPLEX VIRUS 2; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNOHISTOCHEMISTRY; INFECTION; INNATE IMMUNITY; LAMINA PROPRIA; LYMPHOCYTE COUNT; LYMPHOCYTE PROLIFERATION; MACROPHAGE; MAST CELL; MEMORY T LYMPHOCYTE; MOLECULAR DYNAMICS; MULTIPLE SCLEROSIS; MYELIN SHEATH; NATURAL KILLER CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PSORIASIS; REGULATORY T LYMPHOCYTE; REVIEW; RHEUMATOID ARTHRITIS; SIMIAN IMMUNODEFICIENCY VIRUS; SYSTEMIC SCLEROSIS; T LYMPHOCYTE; TRYPANOSOMA CRUZI; ULCERATIVE COLITIS; UPREGULATION; VIRUS LOAD; VIRUS REPLICATION; VIRUS TRANSMISSION;

ANIMALS; COMMUNICABLE DISEASES; HUMANS; IMMUNE SYSTEM; IMMUNE SYSTEM DISEASES; IMMUNOTHERAPY; INTERLEUKIN-15; MODELS, BIOLOGICAL; MOLECULAR TARGETED THERAPY;

EID: 79952246247     PISSN: 13596101     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cytogfr.2010.09.003     Document Type: Review

References (145)

1. Budagian V., Bulanova E., Paus R., Bulfone-Paus S. IL-15/IL-15 receptor biology: a guided tour through an expanding universe. Cytokine Growth Factor Rev 2006, 17:259-280.
2. Wang X., Lupardus P., Laporte S.L., Garcia K.C. Structural biology of shared cytokine receptors. Annu Rev Immunol 2009, 27:29-60.
3. Carroll H.P., Paunovic V., Gadina M. Signalling, inflammation and arthritis: Crossed signals: the role of interleukin-15 and -18 in autoimmunity. Rheumatology (Oxford) 2008, 47:1269-1277.
4. Stonier S.W., Schluns K.S. Trans-presentation: a novel mechanism regulating IL-15 delivery and responses. Immunol Lett 2010, 127:85-92.
5. Fehniger T.A., Suzuki K., Ponnappan A., VanDeusen J.B., Cooper M.A., Florea S.M., et al. Fatal leukemia in interleukin 15 transgenic mice follows early expansions in natural killer and memory phenotype CD8+ T cells. J Exp Med 2001, 193:219-231.
6. Ma A., Koka R., Burkett P. Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Annu Rev Immunol 2006, 24:657-679.
7. Mortier E., Woo T., Advincula R., Gozalo S., Ma A. IL-15Ralpha chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation. J Exp Med 2008, 205:1213-1225.
8. Castillo E.F., Stonier S.W., Frasca L., Schluns K.S. Dendritic cells support the in vivo development and maintenance of NK cells via IL-15 trans-presentation. J Immunol 2009, 183:4948-4956.
9. Fehniger T.A., Caligiuri M.A. Interleukin 15: biology and relevance to human disease. Blood 2001, 97:14-32.
10. Dubois S.P., Waldmann T.A., Müller J.R. Survival adjustment of mature dendritic cells by IL-15. Proc Natl Acad Sci USA 2005, 102:8662-8667.
11. Cassatella M.A., McDonald P.P. Interleukin-15 and its impact on neutrophil function. Curr Opin Hematol 2000, 7:174-177.
12. Hoontrakoon R., Chu H.W., Gardai S.J., Wenzel S.E., McDonald P., Fadok V.A., et al. Interleukin-15 inhibits spontaneous apoptosis in human eosinophils via autocrine production of granulocyte macrophage-colony stimulating factor and nuclear factor-kappaB activation. Am J Respir Cell Mol Biol 2002, 26:404-412.
13. Masuda A., Matsuguchi T., Yamaki K., Hayakawa T., Yoshikai Y. Interleukin-15 prevents mouse mast cell apoptosis through STAT6-mediated Bcl-xL expression. J Biol Chem 2001, 276:26107-26113.
14. Waldmann T.A. The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat Rev Immunol 2006, 6:595-601.
15. Kennedy M.K., Glaccum M., Brown S.N., Butz E.A., Viney J.L., Embers M., et al. Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med 2000, 191:771-780.
16. Lodolce J.P., Boone D.L., Chai S., Swain R.E., Dassopoulos T., Trettin S., et al. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity 1998, 9:669-676.
17. Suzuki H., Duncan G.S., Takimoto H., Mak T.W. Abnormal development of intestinal intraepithelial lymphocytes and peripheral natural killer cells in mice lacking the IL-2 receptor beta chain. J Exp Med 1997, 185:499-505.
18. Schluns K.S., Nowak E.C., Cabrera-Hernandez A., Puddington L., Lefrançois L., Aguila H.L. Distinct cell types control lymphoid subset development by means of IL-15 and IL-15 receptor alpha expression. Proc Natl Acad Sci USA 2004, 101:5616-5621.
19. Ma L.J., Acero L.F., Zal T., Schluns K.S. Trans-presentation of IL-15 by intestinal epithelial cells drives development of CD8alphaalpha IELs. J Immunol 2009, 183:1044-1054.
20. van Leeuwen E.M., Sprent J., Surh C.D. Generation and maintenance of memory CD4(+) T cells. Curr Opin Immunol 2009, 21:167-172.
21. Osborne L.C., Abraham N. Regulation of memory T cells by gammac cytokines. Cytokine 2010, 50:105-113.
22. Schluns K.S., Williams K., Ma A., Zheng X.X., Lefrançois L. Cutting edge: requirement for IL-15 in the generation of primary and memory antigen-specific CD8 T cells. J Immunol 2002, 168:4827-4831.
23. Becker T.C., Wherry E.J., Boone D., Murali-Krishna K., Antia R., Ma A., et al. Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells. J Exp Med 2002, 195:1541-1548.
24. Burkett P.R., Koka R., Chien M., Chai S., Chan F., Ma A., et al. IL-15R alpha expression on CD8+ T cells is dispensable for T cell memory. Proc Natl Acad Sci USA 2003, 100:4724-4729.
25. Stonier S.W., Ma L.J., Castillo E.F., Schluns K.S. Dendritic cells drive memory CD8 T-cell homeostasis via IL-15 transpresentation. Blood 2008, 112:4546-4554.
26. Mortier E., Advincula R., Kim L., Chmura S., Barrera J., Reizis B., et al. Macrophage- and dendritic-cell-derived interleukin-15 receptor alpha supports homeostasis of distinct CD8+ T cell subsets. Immunity 2009, 31:811-822.
27. Rochman Y., Spolski R., Leonard W.J. New insights into the regulation of T cells by gamma(c) family cytokines. Nat Rev Immunol 2009, 9:480-490.
28. Imamichi H., Sereti I., Lane H.C. IL-15 acts as a potent inducer of CD4(+)CD25(hi) cells expressing FOXP3. Eur J Immunol 2008, 38:1621-1630.
29. Annunziato F., Cosmi L., Santarlasci V., Maggi L., Liotta F., Mazzinghi B., et al. Phenotypic and functional features of human Th17 cells. J Exp Med 2007, 204:1849-1861.
30. Nady S., Ignatz-Hoover J., Shata M.T. Interleukin-12 is the optimum cytokine to expand human Th17 cells in vitro. Clin Vaccine Immunol 2009, 16:798-805.
31. Gill N., Paltser G., Ashkar A.A. Interleukin-15 expression affects homeostasis and function of B cells through NK cell-derived interferon-gamma. Cell Immunol 2009, 258:59-64.
32. Di Sabatino A., Corazza G.R. Coeliac disease. Lancet 2009, 373:1480-1493.
33. Meresse B., Ripoche J., Heyman M., Cerf-Bensussan N. Celiac disease: from oral tolerance to intestinal inflammation, autoimmunity and lymphomagenesis. Mucosal Immunol 2009, 2:8-23.
34. Ciccocioppo R., Di Sabatino A., Parroni R., Dálò S., Pistoia M.A., Doglioni C., et al. Cytolytic mechanisms of intraepithelial lymphocytes in coeliac disease (CoD). Clin Exp Immunol 2000, 120:235-240.
35. Ciccocioppo R., Di Sabatino A., Parroni R., Muzi P., Dálò S., Ventura T., et al. Increased enterocyte apoptosis and Fas-Fas ligand system in celiac disease. Am J Clin Pathol 2001, 115:494-503.
36. Mention J.J., Ben Ahmed M., Bègue B., Barbe U., Verkarre V., Asnafi V., et al. Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease. Gastroenterology 2003, 125:730-745.
37. Jabri B., de Serre N.P., Cellier C., Evans K., Gache C., Carvalho C., et al. Selective expansion of intraepithelial lymphocytes expressing the HLA-E-specific natural killer receptor CD94 in celiac disease. Gastroenterology 2000, 118:867-879.
38. Hüe S., Mention J.J., Monteiro R.C., Zhang S., Cellier C., Schmitz J., et al. A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease. Immunity 2004, 21:367-377.
39. Halttunen T., Mäki M. Serum immunoglobulin A from patients with celiac disease inhibits human T84 intestinal crypt epithelial cell differentiation. Gastroenterology 1999, 116:566-572.
40. Maiuri L., Ciacci C., Auricchio S., Brown V., Quaratino S., Londei M. Interleukin 15 mediates epithelial changes in celiac disease. Gastroenterology 2000, 119:996-1006.
41. Benahmed M., Meresse B., Arnulf B., Barbe U., Mention J.J., Verkarre V., et al. Inhibition of TGF-beta signaling by IL-15: a new role for IL-15 in the loss of immune homeostasis in celiac disease. Gastroenterology 2007, 132:994-1008.
42. Di Sabatino A., Ciccocioppo R., Cupelli F., Cinque B., Millimaggi D., Clarkson M.M., et al. Epithelium derived interleukin 15 regulates intraepithelial lymphocyte Th1 cytokine production, cytotoxicity, and survival in coeliac disease. Gut 2006, 55:469-477.
43. van Heel D.A. Interleukin 15: its role in intestinal inflammation. Gut 2006, 55:444-445.
44. Malamut G., El Machhour R., Montcuquet N., Martin-Lannerée S., Dusanter-Fourt I., Verkarre V., et al. IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease-associated inflammation and lymphomagenesis. J Clin Invest 2010, 120:2131-2143.
45. Di Sabatino A., Pickard K.M., Gordon J.N., Salvati V., Mazzarella G., Beattie R.M., et al. Evidence for the role of interferon-alfa production by dendritic cells in the Th1 response in celiac disease. Gastroenterology 2007, 133:1175-1187.
46. Fina D., Sarra M., Caruso R., Del Vecchio Blanco G., Pallone F., MacDonald T.T., et al. Interleukin 21 contributes to the mucosal T helper cell type 1 response in coeliac disease. Gut 2008, 57:887-892.
47. De Nitto D., Monteleone I., Franzè E., Pallone F., Monteleone G. Involvement of interleukin-15 and interleukin-21, two gamma-chain-related cytokines, in celiac disease. World J Gastroenterol 2009, 15:4609-4614.
48. Peluso I., Fantini M.C., Fina D., Caruso R., Boirivant M., MacDonald T.T., et al. IL-21 counteracts the regulatory T cell-mediated suppression of human CD4+ T lymphocytes. J Immunol 2007, 178:732-739.
49. Baumgart D.C., Sandborn W.J. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet 2007, 369:1641-1657.
50. Macdonald T.T., Monteleone G. Immunity, inflammation, and allergy in the gut. Science 2005, 307:1920-1925.
51. Ohta N., Hiroi T., Kweon M.N., Kinoshita N., Jang M.H., Mashimo T., et al. IL-15-dependent activation-induced cell death-resistant Th1 type CD8 alpha beta+NK1.1+ T cells for the development of small intestinal inflammation. J Immunol 2002, 169:460-468.
52. Yoshihara K., Yajima T., Kubo C., Yoshikai Y. Role of interleukin 15 in colitis induced by dextran sulphate sodium in mice. Gut 2006, 55:334-341.
53. Liu Z., Geboes K., Colpaert S., D'Haens G.R., Rutgeerts P., Ceuppens J.L. IL-15 is highly expressed in inflammatory bowel disease and regulates local T cell-dependent cytokine production. J Immunol 2000, 164:3608-3615.
54. Nishiwaki T., Ina K., Goto H., Watanabe O., Tsuzuki T., Furuta R., et al. Possible involvement of the interleukin-15 and interleukin-15 receptor system in a heightened state of lamina propria B cell activation and differentiation in patients with inflammatory bowel disease. J Gastroenterol 2005, 40:128-136.
55. Allez M., Tieng V., Nakazawa A., Treton X., Pacault V., Dulphy N., et al. CD4+NKG2D+ T cells in Crohn's disease mediate inflammatory and cytotoxic responses through MICA interactions. Gastroenterology 2007, 132:2346-2358.
56. León A.J., Gómez E., Garrote J.A., Bernardo D., Barrera A., Marcos J.L., et al. High levels of proinflammatory cytokines, but not markers of tissue injury, in unaffected intestinal areas from patients with IBD. Mediators Inflamm 2009, 2009:580450.
57. Bouchaud G., Mortier E., Flamant M., Barbieux I., Plet A., Galmiche J.P., et al. Interleukin-15 and its soluble receptor mediate the response to infliximab in patients with Crohn's disease. Gastroenterology 2010, 138:2378-2387.
58. Sospedra M., Martin R. Immunology of multiple sclerosis. Annu Rev Immunol 2005, 23:683-747.
59. Gomez-Nicola D., Spagnolo A., Guaza C., Nieto-Sampedro M. Aggravated experimental autoimmune encephalomyelitis in IL-15 knockout mice. Exp Neurol 2010, 222:235-242.
60. Wu X., Pan W., He Y., Hsuchou H., Kastin A.J. Cerebral interleukin-15 shows upregulation and beneficial effects in experimental autoimmune encephalomyelitis. J Neuroimmunol 2010, 223:65-72.
61. Rentzos M., Cambouri C., Rombos A., Nikolaou C., Anagnostouli M., Tsoutsou A., et al. IL-15 is elevated in serum and cerebrospinal fluid of patients with multiple sclerosis. J Neurol Sci 2006, 241:25-29.
62. Correale J., Villa A. Isolation and characterization of CD8+ regulatory T cells in multiple sclerosis. J Neuroimmunol 2008, 195:121-134.
63. Vaknin-Dembinsky A., Brass S.D., Gandhi R., Weiner H.L. Membrane bound IL-15 is increased on CD14 monocytes in early stages of MS. J Neuroimmunol 2008, 195:135-139.
64. Jinnin M. Mechanisms of skin fibrosis in systemic sclerosis. J Dermatol 2010, 37:11-25.
65. Yamamoto T. Animal model of systemic sclerosis. J Dermatol 2010, 37:26-41.
66. Wang H.W., Tedla N., Hunt J.E., Wakefield D., McNeil H.P. Mast cell accumulation and cytokine expression in the tight skin mouse model of scleroderma. Exp Dermatol 2005, 14:295-302.
67. Wuttge D.M., Wildt M., Geborek P., Wollheim F.A., Scheja A., Akesson A. Serum IL-15 in patients with early systemic sclerosis: a potential novel marker of lung disease. Arthritis Res Ther 2007, 9:R85.
68. Beirne P., Pantelidis P., Charles P., Wells A.U., Abraham D.J., Denton C.P., et al. Multiplex immune serum biomarker profiling in sarcoidosis and systemic sclerosis. Eur Respir J 2009, 34:1376-1382.
69. Joseph A., Brasington R., Kahl L., Ranganathan P., Cheng T.P., Atkinson J. Immunologic rheumatic disorders. J Allergy Clin Immunol 2010, 125:S204-S215.
70. McInnes I.B., Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 2007, 7:429-442.
71. Kim H.R., Hwang K.A., Park S.H., Kang I. IL-7 and IL-15: biology and roles in T-Cell immunity in health and disease. Crit Rev Immunol 2008, 28:325-339.
72. Yamada H., Kaibara N., Okano S., Maeda T., Shuto T., Nakashima Y., et al. Interleukin-15 selectively expands CD57+ CD28- CD4+ T cells, which are increased in active rheumatoid arthritis. Clin Immunol 2007, 124:328-335.
73. Verri W.A., Cunha T.M., Ferreira S.H., Wei X., Leung B.P., Fraser A., et al. IL-15 mediates antigen-induced neutrophil migration by triggering IL-18 production. Eur J Immunol 2007, 37:3373-3380.
74. Nestle F.O., Kaplan D.H., Barker J. Psoriasis. N Engl J Med 2009, 361:496-509.
75. Rückert R., Asadullah K., Seifert M., Budagian V.M., Arnold R., Trombotto C., et al. Inhibition of keratinocyte apoptosis by IL-15: a new parameter in the pathogenesis of psoriasis?. J Immunol 2000, 165:2240-2250.
76. Ong P.Y., Hamid Q.A., Travers J.B., Strickland I., Al Kerithy M., Boguniewicz M., et al. Decreased IL-15 may contribute to elevated IgE and acute inflammation in atopic dermatitis. J Immunol 2002, 168:505-510.
77. Elder J.T. IL-15 and psoriasis: another genetic link to Th17?. J Invest Dermatol 2007, 127:2495-2497.
78. Duffin K.C., Krueger G.G. Genetic variations in cytokines and cytokine receptors associated with psoriasis found by genome-wide association. J Invest Dermatol 2009, 129:827-833.
79. Mattapallil J.J., Douek D.C., Hill B., Nishimura Y., Martin M., Roederer M. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 2005, 434:1093-1097.
80. Eberly M.D., Kader M., Hassan W., Rogers K.A., Zhou J., Mueller Y.M., et al. Increased IL-15 production is associated with higher susceptibility of memory CD4 T cells to simian immunodeficiency virus during acute infection. J Immunol 2009, 182:1439-1448.
81. Mueller Y.M., Do D.H., Altork S.R., Artlett C.M., Gracely E.J., Katsetos C.D., et al. IL-15 treatment during acute simian immunodeficiency virus (SIV) infection increases viral set point and accelerates disease progression despite the induction of stronger SIV-specific CD8+ T cell responses. J Immunol 2008, 180:350-360.
82. Calarota S.A., Otero M., Hermanstyne K., Lewis M., Rosati M., Felber B.K., et al. Use of interleukin 15 to enhance interferon-gamma production by antigen-specific stimulated lymphocytes from rhesus macaques. J Immunol Methods 2003, 279:55-67.
83. Mueller Y.M., Petrovas C., Do D.H., Altork S.R., Fischer-Smith T., Rappaport J., et al. Early establishment and antigen dependence of simian immunodeficiency virus-specific CD8+ T-cell defects. J Virol 2007, 81:10861-10868.
84. Mueller Y.M., Petrovas C., Bojczuk P.M., Dimitriou I.D., Beer B., Silvera P., et al. Interleukin-15 increases effector memory CD8+ t cells and NK Cells in simian immunodeficiency virus-infected macaques. J Virol 2005, 79:4877-4885.
85. Leone A., Picker L.J., Sodora D.L. IL-2, IL-7 and IL-15 as immuno-modulators during SIV/HIV vaccination and treatment. Curr HIV Res 2009, 7:83-90.
86. Picker L.J., Reed-Inderbitzin E.F., Hagen S.I., Edgar J.B., Hansen S.G., Legasse A., et al. IL-15 induces CD4 effector memory T cell production and tissue emigration in nonhuman primates. J Clin Invest 2006, 116:1514-1524.
87. Ward J., Barker E. Role of natural killer cells in HIV pathogenesis. Curr HIV/AIDS Rep 2008, 5:44-50.
88. d'Ettorre G., Andreotti M., Carnevalini M., Andreoni C., Zaffiri L., Vullo V., et al. Interleukin-15 enhances the secretion of IFN-gamma and CC chemokines by natural killer cells from HIV viremic and aviremic patients. Immunol Lett 2006, 103:192-195.
89. Boulassel M.R., Young M., Routy J.P., Sekaly R.P., Tremblay C., Rouleau D. Circulating levels of IL-7 but not IL-15, IGF-1, and TGF-beta are elevated during primary HIV-1 infection. HIV Clin Trials 2004, 5:357-359.
90. Stacey A.R., Norris P.J., Qin L., Haygreen E.A., Taylor E., Heitman J., et al. Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections. J Virol 2009, 83:3719-3733.
91. Roberts L., Passmore J.A., Williamson C., Little F., Bebell L.M., Mlisana K., et al. Plasma cytokine levels during acute HIV-1 infection predict HIV disease progression. AIDS 2010, 24:819-831.
92. Amicosante M., Poccia F., Gioia C., Montesano C., Topino S., Martini F., et al. Levels of interleukin-15 in plasma may predict a favorable outcome of structured treatment interruption in patients with chronic human immunodeficiency virus infection. J Infect Dis 2003, 188:661-665.
93. Ahmad R., Sindhu S.T., Toma E., Morisset R., Ahmad A. Studies on the production of IL-15 in HIV-infected/AIDS patients. J Clin Immunol 2003, 23:81-90.
94. Biancotto A., Grivel J.C., Iglehart S.J., Vanpouille C., Lisco A., Sieg S.F., et al. Abnormal activation and cytokine spectra in lymph nodes of people chronically infected with HIV-1. Blood 2007, 109:4272-4279.
95. d'Ettorre G., Forcina G., Lichtner M., Mengoni F., D'Agostino C., Massetti A.P., et al. Interleukin-15 in HIV infection: immunological and virological interactions in antiretroviral-naive and -treated patients. AIDS 2002, 16:181-188.
96. Walter J., Ghosh M.K., Kuhn L., Semrau K., Sinkala M., Kankasa C., et al. High concentrations of interleukin 15 in breast milk are associated with protection against postnatal HIV transmission. J Infect Dis 2009, 200:1498-1502.
97. Sabbaj S., Ghosh M.K., Edwards B.H., Leeth R., Decker W.D., Goepfert P.A., et al. Breast milk-derived antigen-specific CD8+ T cells: an extralymphoid effector memory cell population in humans. J Immunol 2005, 174:2951-2956.
98. Rousseau C.M., Nduati R.W., Richardson B.A., Steele M.S., John-Stewart G.C., Mbori-Ngacha D.A., et al. Longitudinal analysis of human immunodeficiency virus type 1 RNA in breast milk and of its relationship to infant infection and maternal disease. J Infect Dis 2003, 187:741-747.
99. Ahmad A., Ahmad R., Iannello A., Toma E., Morisset R., Sindhu S.T. IL-15 and HIV infection: lessons for immunotherapy and vaccination. Curr HIV Res 2005, 3:261-270.
100. Sirskyj D., Thèze J., Kumar A., Kryworuchko M. Disruption of the gamma c cytokine network in T cells during HIV infection. Cytokine 2008, 43:1-14.
101. Azimi N., Mariner J., Jacobson S., Waldmann T.A. How does interleukin 15 contribute to the pathogenesis of HTLV type 1-associated myelopathy/tropical spastic paraparesis?. AIDS Res Hum Retroviruses 2000, 16:1717-1722.
102. Enose-Akahata Y., Oh U., Grant C., Jacobson S. Retrovirally induced CTL degranulation mediated by IL-15 expression and infection of mononuclear phagocytes in patients with HTLV-I-associated neurologic disease. Blood 2008, 112:2400-2410.
103. Gill N., Ashkar A.A. Adaptive immune responses fail to provide protection against genital HSV-2 infection in the absence of IL-15. Eur J Immunol 2007, 37:2529-2538.
104. Gill N., Rosenthal K.L., Ashkar A.A. NK and NKT cell-independent contribution of interleukin-15 to innate protection against mucosal viral infection. J Virol 2005, 79:4470-4478.
105. Gill N., Ashkar A.A. Overexpression of interleukin-15 compromises CD4-dependent adaptive immune responses against herpes simplex virus 2. J Virol 2009, 83:918-926.
106. Kagimoto Y., Yamada H., Ishikawa T., Maeda N., Goshima F., Nishiyama Y., et al. A regulatory role of interleukin 15 in wound healing and mucosal infection in mice. J Leukoc Biol 2008, 83:165-172.
107. Rehermann B., Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol 2005, 5:215-229.
108. Bertoletti A., Gehring A.J. The immune response during hepatitis B virus infection. J Gen Virol 2006, 87:1439-1449.
109. Dunn C., Peppa D., Khanna P., Nebbia G., Jones M., Brendish N., et al. Temporal analysis of early immune responses in patients with acute hepatitis B virus infection. Gastroenterology 2009, 137:1289-1300.
110. Meier U.C., Owen R.E., Taylor E., Worth A., Naoumov N., Willberg C., et al. Shared alterations in NK cell frequency, phenotype, and function in chronic human immunodeficiency virus and hepatitis C virus infections. J Virol 2005, 79:12365-12374.
111. Nguyen K.B., Salazar-Mather T.P., Dalod M.Y., Van Deusen J.B., Wei X.Q., Liew F.Y., et al. Coordinated and distinct roles for IFN-alpha beta, IL-12, and IL-15 regulation of NK cell responses to viral infection. J Immunol 2002, 169:4279-4287.
112. Jinushi M., Takehara T., Tatsumi T., Kanto T., Groh V., Spies T., et al. Autocrine/paracrine IL-15 that is required for type I IFN-mediated dendritic cell expression of MHC class I-related chain A and B is impaired in hepatitis C virus infection. J Immunol 2003, 171:5423-5429.
113. Yajima T., Yoshihara K., Nakazato K., Kumabe S., Koyasu S., Sad S., et al. IL-15 regulates CD8+ T cell contraction during primary infection. J Immunol 2006, 176:507-515.
114. Jabbari A., Harty J.T. Secondary memory CD8+ T cells are more protective but slower to acquire a central-memory phenotype. J Exp Med 2006, 203:919-932.
115. Sandau M.M., Kohlmeier J.E., Woodland D.L., Jameson S.C. IL-15 regulates both quantitative and qualitative features of the memory CD8 T cell pool. J Immunol 2010, 184:35-44.
116. Saito K., Yajima T., Kumabe S., Doi T., Yamada H., Sad S., et al. Impaired protection against Mycobacterium bovis bacillus Calmette-Guerin infection in IL-15-deficient mice. J Immunol 2006, 176:2496-2504.
117. Tang C., Yamada H., Shibata K., Yoshida S., Wajjwalku W., Yoshikai Y. IL-15 protects antigen-specific CD8+ T cell contraction after Mycobacterium bovis bacillus Calmette-Guérin infection. J Leukoc Biol 2009, 86:187-194.
118. Ashkar A.A., Reid S., Verdu E.F., Zhang K., Coombes B.K. Interleukin-15 and NK1.1+ cells provide innate protection against acute Salmonella enterica serovar Typhimurium infection in the gut and in systemic tissues. Infect Immun 2009, 77:214-222.
119. Hiromatsu T., Yajima T., Matsuguchi T., Nishimura H., Wajjwalku W., Arai T., et al. Overexpression of interleukin-15 protects against Escherichia coli-induced shock accompanied by inhibition of tumor necrosis factor-alpha-induced apoptosis. J Infect Dis 2003, 187:1442-1451.
120. Orinska Z., Maurer M., Mirghomizadeh F., Bulanova E., Metz M., Nashkevich N., et al. IL-15 constrains mast cell-dependent antibacterial defenses by suppressing chymase activities. Nat Med 2007, 13:927-934.
121. Ward P.A. The curiosity of IL-15. Nat Med 2007, 13:903-904.
122. Padilla A.M., Bustamante J.M., Tarleton R.L. CD8+ T cells in Trypanosoma cruzi infection. Curr Opin Immunol 2009, 21:385-390.
123. Bixby L.M., Tarleton R.L. Stable CD8+ T cell memory during persistent Trypanosoma cruzi infection. J Immunol 2008, 181:2644-2650.
124. Fonseca S.G., Reis M.M., Coelho V., Nogueira L.G., Monteiro S.M., Mairena E.C., et al. Locally produced survival cytokines IL-15 and IL-7 may be associated to the predominance of CD8+ T cells at heart lesions of human chronic Chagas disease cardiomyopathy. Scand J Immunol 2007, 66:362-371.
125. Lieberman L.A., Villegas E.N., Hunter C.A. Interleukin-15-deficient mice develop protective immunity to Toxoplasma gondii. Infect Immun 2004, 72:6729-6732.
126. Combe C.L., Moretto M.M., Schwartzman J.D., Gigley J.P., Bzik D.J., Khan I.A. Lack of IL-15 results in the suboptimal priming of CD4+ T cell response against an intracellular parasite. Proc Natl Acad Sci USA 2006, 103:6635-6640.
127. Villadsen L.S., Schuurman J., Beurskens F., Dam T.N., Dagnaes-Hansen F., Skov L., et al. Resolution of psoriasis upon blockade of IL-15 biological activity in a xenograft mouse model. J Clin Invest 2003, 112:1571-1580.
128. Ferrari-Lacraz S., Zanelli E., Neuberg M., Donskoy E., Kim Y.S., Zheng X.X., et al. Targeting IL-15 receptor-bearing cells with an antagonist mutant IL-15/Fc protein prevents disease development and progression in murine collagen-induced arthritis. J Immunol 2004, 173:5818-5826.
129. Baslund B., Tvede N., Danneskiold-Samsoe B., Larsson P., Panayi G., Petersen J., et al. Targeting interleukin-15 in patients with rheumatoid arthritis: a proof-of-concept study. Arthritis Rheum 2005, 52:2686-2692.
130. Gabay C., McInnes I.B. The biological and clinical importance of the 'new generation' cytokines in rheumatic diseases. Arthritis Res Ther 2009, 11:230.
131. Atzeni F., Sarzi-Puttini P. Anti-cytokine antibodies for rheumatic diseases. Curr Opin Investig Drugs 2009, 10:1204-1211.
132. Ghoreschi K., Laurence A., O'Shea J.J. Selectivity and therapeutic inhibition of kinases: to be or not to be?. Nat Immunol 2009, 10:356-360.
133. West K. CP-690550, a JAK3 inhibitor as an immunosuppressant for the treatment of rheumatoid arthritis, transplant rejection, psoriasis and other immune-mediated disorders. Curr Opin Investig Drugs 2009, 10:491-504.
134. Chang B.Y., Zhao F., He X., Ren H., Braselmann S., Taylor V., et al. JAK3 inhibition significantly attenuates psoriasiform skin inflammation in CD18 mutant PL/J mice. J Immunol 2009, 183:2183-2192.
135. Yokoyama S., Watanabe N., Sato N., Perera P.Y., Filkoski L., Tanaka T., et al. Antibody-mediated blockade of IL-15 reverses the autoimmune intestinal damage in transgenic mice that overexpress IL-15 in enterocytes. Proc Natl Acad Sci USA 2009, 106:15849-15854.
136. Calarota S.A., Weiner D.B. Enhancement of human immunodeficiency virus type 1-DNA vaccine potency through incorporation of T-helper 1 molecular adjuvants. Immunol Rev 2004, 199:84-99.
137. Chabalgoity J.A., Baz A., Rial A., Grille S. The relevance of cytokines for development of protective immunity and rational design of vaccines. Cytokine Growth Factor Rev 2007, 18:195-207.
138. Rodrigues L., Bonorino C. Role of IL-15 and IL-21 in viral immunity: applications for vaccines and therapies. Expert Rev Vaccines 2009, 8:167-177.
139. Kutzler M.A., Robinson T.M., Chattergoon M.A., Choo D.K., Choo A.Y., Choe P.Y., et al. Coimmunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help. J Immunol 2005, 175:112-123.
140. Boyer J.D., Robinson T.M., Kutzler M.A., Vansant G., Hokey D.A., Kumar S., et al. Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid. Proc Natl Acad Sci USA 2007, 104:18648-18653.
141. Chong S.Y., Egan M.A., Kutzler M.A., Megati S., Masood A., Roopchard V., et al. Comparative ability of plasmid IL-12 and IL-15 to enhance cellular and humoral immune responses elicited by a SIVgag plasmid DNA vaccine and alter disease progression following SHIV(89.6P) challenge in rhesus macaques. Vaccine 2007, 25:4967-4982.
142. Hryniewicz A., Price D.A., Moniuszko M., Boasso A., Edghill-Spano Y., West S.M., et al. Interleukin-15 but not interleukin-7 abrogates vaccine-induced decrease in virus level in simian immunodeficiency virus mac251-infected macaques. J Immunol 2007, 178:3492-3504.
143. Demberg T., Boyer J.D., Malkevich N., Patterson L.J., Venzon D., Summers E.L., et al. Sequential priming with simian immunodeficiency virus (SIV) DNA vaccines, with or without encoded cytokines, and a replicating adenovirus-SIV recombinant followed by protein boosting does not control a pathogenic SIVmac251 mucosal challenge. J Virol 2008, 82:10911-10921.
144. Dubie R.A., Maksaereekul S., Shacklett B.L., Lemongello D., Cole K.S., Villinger F., et al. Co-immunization with IL-15 enhances cellular immune responses induced by a vif-deleted simian immunodeficiency virus proviral DNA vaccine and confers partial protection against vaginal challenge with SIVmac251. Virology 2009, 386:109-121.
145. Valentin A., von Gegerfelt A., Rosati M., Miteloudis G., Alicea C., Bergamaschi C., et al. Repeated DNA therapeutic vaccination of chronically SIV-infected macaques provides additional virological benefit. Vaccine 2010, 28:1962-1974.