The role of interleukin-21 in HIV infection

Cytokine and Growth Factor Reviews

Volumn 23, Issue 4-5, 2012, Pages 173-180

  Pallikkuth, Suresh ^a   Parmigiani, Anita ^a   Pahwa, Savita ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

Author keywords

HIV and IL 21; IL 21 and B cells; IL 21 and immunity; IL 21 and T cells; Immunomodulation by IL 21

Indexed keywords

INTERLEUKIN 21; INTERLEUKIN 21 RECEPTOR; RECOMBINANT CYTOKINE; RECOMBINANT INTERLEUKIN 12; RECOMBINANT INTERLEUKIN 15; RECOMBINANT INTERLEUKIN 21; RECOMBINANT INTERLEUKIN 7; UNCLASSIFIED DRUG;

ADAPTIVE IMMUNITY; ANTIGEN PRESENTING CELL; ANTIVIRAL ACTIVITY; ARTICLE; B LYMPHOCYTE; BIOLOGICAL ACTIVITY; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELLULAR DISTRIBUTION; CYTOKINE PRODUCTION; CYTOKINE RELEASE; CYTOKINE RESPONSE; DRUG MEGADOSE; DRUG TOLERABILITY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HUMORAL IMMUNITY; IMMUNE RESPONSE GENE; IMMUNOMODULATION; IMMUNOTHERAPY; INTERLEUKIN 21 RECEPTOR GENE; LYMPHOCYTE DIFFERENTIATION; MEMORY CELL; NATURAL KILLER CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; TH17 CELL;

B-LYMPHOCYTES; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; HIV INFECTIONS; HUMANS; INTERLEUKINS; KILLER CELLS, NATURAL; LYMPHOCYTE ACTIVATION; RECEPTORS, INTERLEUKIN-21;

EID: 84864945744     PISSN: 13596101     EISSN: 18790305     Source Type: Journal    
DOI: 10.1016/j.cytogfr.2012.05.004     Document Type: Article

References (133)

1. Ma J., Ma D., Ji C. The role of IL-21 in hematological malignancies. Cytokine 2011, 56:133-139.
2. Sarra M., Franze E., Pallone F., Monteleone G. Targeting interleukin-21 in inflammatory diseases. Expert Opinion on Therapeutic Targets 2011, 15:695-702.
3. Sondergaard H., Skak K. IL-21: roles in immunopathology and cancer therapy. Tissue Antigens 2009, 74:467-479.
4. Spolski R., Leonard W.J. Interleukin-21: basic biology and implications for cancer and autoimmunity. Annual Review of Immunology 2008, 26:57-79.
5. Yuan F.L., Hu W., Lu W.G., Li X., Li J.P., Xu R.S., et al. Targeting interleukin-21 in rheumatoid arthritis. Molecular Biology Reports 2011, 38:1717-1721.
6. Hashmi M.H., Van Veldhuizen P.J. Interleukin-21: updated review of Phase I and II clinical trials in metastatic renal cell carcinoma, metastatic melanoma and relapsed/refractory indolent non-Hodgkin's lymphoma. Expert Opinion on Biological Therapy 2010, 10:807-817.
7. Davis I.D., Brady B., Kefford R.F., Millward M., Cebon J., Skrumsager B.K., et al. Clinical and biological efficacy of recombinant human interleukin-21 in patients with stage IV malignant melanoma without prior treatment: a phase IIa trial. Clinical Cancer Research 2009, 15:2123-2129.
8. Davis I.D., Skrumsager B.K., Cebon J., Nicholaou T., Barlow J.W., Moller N.P., et al. An open-label, two-arm, phase I trial of recombinant human interleukin-21 in patients with metastatic melanoma. Clinical Cancer Research 2007, 13:3630-3636.
9. Frederiksen K.S., Lundsgaard D., Freeman J.A., Hughes S.D., Holm T.L., Skrumsager B.K., et al. IL-21 induces in vivo immune activation of NK cells and CD8(+) T cells in patients with metastatic melanoma and renal cell carcinoma. Cancer Immunology, Immunotherapy 2008, 57:1439-1449.
10. Thompson J.A., Curti B.D., Redman B.G., Bhatia S., Weber J.S., Agarwala S.S., et al. Phase I study of recombinant interleukin-21 in patients with metastatic melanoma and renal cell carcinoma. Journal of Clinical Oncology 2008, 26:2034-2039.
11. Yi J.S., Ingram J.T., Zajac A.J. IL-21 deficiency influences CD8 T cell quality and recall responses following an acute viral infection. Journal of Immunology 2010, 185:4835-4845.
12. Novy P., Huang X., Leonard W.J., Yang Y. Intrinsic IL-21 signaling is critical for CD8 T cell survival and memory formation in response to vaccinia viral infection. Journal of Immunology 2011, 186:2729-2738.
13. Elsaesser H., Sauer K., Brooks D.G. IL-21 is required to control chronic viral infection. Science 2009, 324:1569-1572.
14. Frohlich A., Kisielow J., Schmitz I., Freigang S., Shamshiev A.T., Weber J., et al. IL-21R on T cells is critical for sustained functionality and control of chronic viral infection. Science 2009, 324:1576-1580.
15. Yi J.S., Du M., Zajac A.J. A vital role for interleukin-21 in the control of a chronic viral infection. Science 2009, 324:1572-1576.
16. Pawlak K., Mysliwiec M., Pawlak D. Interleukin-21 in hemodialyzed patients: association with the etiology of chronic kidney disease and the seropositivity against hepatitis C virus infection. Clinical Biochemistry 2011, 44:1416-1420.
17. Franks I. Viral hepatitis: interleukin 21 has a key role in age-dependent response to HBV. Nature Reviews Gastroenterology & Hepatology 2011, 8:243.
18. Ma S.W., Huang X., Li Y.Y., Tang L.B., Sun X.F., Jiang X.T., et al. High serum IL-21 levels after 12 weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B. Journal of Hepatology 2012, 56:775-781.
19. Publicover J., Goodsell A., Nishimura S., Vilarinho S., Wang Z.E., Avanesyan L., et al. IL-21 is pivotal in determining age-dependent effectiveness of immune responses in a mouse model of human hepatitis B. Journal of Clinical Investigation 2011, 121:1154-1162.
20. Sieg S.F., Bazdar D.A., Harding C.V., Lederman M.M. Differential expression of interleukin-2 and gamma interferon in human immunodeficiency virus disease. Journal of Virology 2001, 75:9983-9985.
21. Giorgi J.V., Hultin L.E., McKeating J.A., Johnson T.D., Owens B., Jacobson L.P., et al. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. Journal of Infectious Diseases 1999, 179:859-870.
22. Chevalier M.F., Julg B., Pyo A., Flanders M., Ranasinghe S., Soghoian D.Z., et al. HIV-1-specific interleukin-21+ CD4+ T cell responses contribute to durable viral control through the modulation of HIV-specific CD8+ T cell function. Journal of Virology 2011, 85:733-741.
23. Iannello A., Boulassel M.R., Samarani S., Debbeche O., Tremblay C., Toma E., et al. Dynamics and consequences of IL-21 production in HIV-infected individuals: a longitudinal and cross-sectional study. Journal of Immunology 2010, 184:114-126.
24. Iannello A., Tremblay C., Routy J.P., Boulassel M.R., Toma E., Ahmad A. Decreased levels of circulating IL-21 in HIV-infected AIDS patients: correlation with CD4+ T-cell counts. Viral Immunology 2008, 21:385-388.
25. Williams L.D., Bansal A., Sabbaj S., Heath S.L., Song W., Tang J., et al. Interleukin-21-producing HIV-1-specific CD8 T cells are preferentially seen in elite controllers. Journal of Virology 2011, 85:2316-2324.
26. Yue F.Y., Lo C., Sakhdari A., Kovacs C.M., Benko E., Liu J., et al. HIV-specific IL-21 producing CD4+ T cells are induced in acute and chronic progressive HIV infection and are associated with relative viral control. Journal of Immunology 2010, 185:498-506.
27. Parrish-Novak J., Dillon S.R., Nelson A., Hammond A., Sprecher C., Gross J.A., et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature 2000, 408:57-63.
28. Parrish-Novak J., Foster D.C., Holly R.D., Clegg C.H. Interleukin-21 and the IL-21 receptor: novel effectors of NK and T cell responses. Journal of Leukocyte Biology 2002, 72:856-863.
29. Coquet J.M., Kyparissoudis K., Pellicci D.G., Besra G., Berzins S.P., Smyth M.J., et al. IL-21 is produced by NKT cells and modulates NKT cell activation and cytokine production. Journal of Immunology 2007, 178:2827-2834.
30. Wei L., Laurence A., Elias K.M., O'Shea J.J. IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner. Journal of Biological Chemistry 2007, 282:34605-34610.
31. Nurieva R.I., Chung Y., Hwang D., Yang X.O., Kang H.S., Ma L., et al. Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity 2008, 29:138-149.
32. Asao H., Okuyama C., Kumaki S., Ishii N., Tsuchiya S., Foster D., et al. Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex. Journal of Immunology 2001, 167:1-5.
33. Ozaki K., Kikly K., Michalovich D., Young P.R., Leonard W.J. Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain. Proceedings of the National Academy of Sciences of the United States of America 2000, 97:11439-11444.
34. Fuqua C.F., Akomeah R., Price J.O., Adunyah S.E. Involvement of ERK-1/2 in IL-21-induced cytokine production in leukemia cells and human monocytes. Cytokine 2008, 44:101-107.
35. Hinrichs C.S., Spolski R., Paulos C.M., Gattinoni L., Kerstann K.W., Palmer D.C., et al. IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy. Blood 2008, 111:5326-5333.
36. Ozaki K., Spolski R., Ettinger R., Kim H.P., Wang G., Qi C.F., et al. Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. Journal of Immunology 2004, 173:5361-5371.
37. Jin H., Carrio R., Yu A., Malek T.R. Distinct activation signals determine whether IL-21 induces B cell costimulation, growth arrest, or Bim-dependent apoptosis. Journal of Immunology 2004, 173:657-665.
38. Brandt K., Bulfone-Paus S., Jenckel A., Foster D.C., Paus R., Ruckert R. Interleukin-21 inhibits dendritic cell-mediated T cell activation and induction of contact hypersensitivity in vivo. Journal of Investigative Dermatology 2003, 121:1379-1382.
39. Caruso R., Fina D., Peluso I., Fantini M.C., Tosti C., Del Vecchio Blanco G., et al. IL-21 is highly produced in Helicobacter pylori-infected gastric mucosa and promotes gelatinases synthesis. Journal of Immunology 2007, 178:5957-5965.
40. Monteleone G., Caruso R., Fina D., Peluso I., Gioia V., Stolfi C., et al. Control of matrix metalloproteinase production in human intestinal fibroblasts by interleukin 21. Gut 2006, 55:1774-1780.
41. Ruckert R., Bulfone-Paus S., Brandt K. Interleukin-21 stimulates antigen uptake, protease activity, survival and induction of CD4+ T cell proliferation by murine macrophages. Clinical and Experimental Immunology 2008, 151:487-495.
42. Chtanova T., Tangye S.G., Newton R., Frank N., Hodge M.R., Rolph M.S., et al. T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells. Journal of Immunology 2004, 173:68-78.
43. Vinuesa C.G., Tangye S.G., Moser B., Mackay C.R. Follicular B helper T cells in antibody responses and autoimmunity. Nature Reviews Immunology 2005, 5:853-865.
44. Vinuesa C.G., Cook M.C., Angelucci C., Athanasopoulos V., Rui L., Hill K.M., et al. A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity. Nature 2005, 435:452-458.
45. Rasheed A.U., Rahn H.P., Sallusto F., Lipp M., Muller G. Follicular B helper T cell activity is confined to CXCR5(hi)ICOS(hi) CD4 T cells and is independent of CD57 expression. European Journal of Immunology 2006, 36:1892-1903.
46. Kroenke M.A., Eto D., Locci M., Cho M., Davidson T., Haddad E.K., et al. Bcl6 and maf cooperate to instruct human follicular helper CD4 T cell differentiation. Journal of Immunology 2012, 188:3734-3744.
47. Bauquet A.T., Jin H., Paterson A.M., Mitsdoerffer M., Ho I.C., Sharpe A.H., et al. The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells. Nature Immunology 2009, 10:167-175.
48. Hiramatsu Y., Suto A., Kashiwakuma D., Kanari H., Kagami S., Ikeda K., et al. c-Maf activates the promoter and enhancer of the IL-21 gene, and TGF-beta inhibits c-Maf-induced IL-21 production in CD4+ T cells. Journal of Leukocyte Biology 2010, 87:703-712.
49. Pot C., Jin H., Awasthi A., Liu S.M., Lai C.Y., Madan R., et al. Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells. Journal of Immunology 2009, 183:797-801.
50. Nurieva R.I., Chung Y., Martinez G.J., Yang X.O., Tanaka S., Matskevitch T.D., et al. Bcl6 mediates the development of T follicular helper cells. Science 2009, 325:1001-1005.
51. Crotty S. Follicular helper CD4 T cells (TFH). Annual Review of Immunology 2011, 29:621-663.
52. Fazilleau N., Mark L., McHeyzer-Williams L.J., McHeyzer-Williams M.G. Follicular helper T cells: lineage and location. Immunity 2009, 30:324-335.
53. Ettinger R., Sims G.P., Fairhurst A.M., Robbins R., da Silva Y.S., Spolski R., et al. IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells. Journal of Immunology 2005, 175:7867-7879.
54. Good K.L., Bryant V.L., Tangye S.G. Kinetics of human B cell behavior and amplification of proliferative responses following stimulation with IL-21. Journal of Immunology 2006, 177:5236-5247.
55. Pene J., Gauchat J.F., Lecart S., Drouet E., Guglielmi P., Boulay V., et al. Cutting edge: IL-21 is a switch factor for the production of IgG1 and IgG3 by human B cells. Journal of Immunology 2004, 172:5154-5157.
56. Morita R., Schmitt N., Bentebibel S.E., Ranganathan R., Bourdery L., Zurawski G., et al. Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity 2011, 34:108-121.
57. Bossaller L., Burger J., Draeger R., Grimbacher B., Knoth R., Plebani A., et al. ICOS deficiency is associated with a severe reduction of CXCR5+CD4 germinal center Th cells. Journal of Immunology 2006, 177:4927-4932.
58. Dong C. TH17 cells in development: an updated view of their molecular identity and genetic programming. Nature Reviews Immunology 2008, 8:337-348.
59. Korn T., Oukka M., Kuchroo V., Bettelli E. Th17 cells: effector T cells with inflammatory properties. Seminars in Immunology 2007, 19:362-371.
60. Hoeve M.A., Savage N.D., de Boer T., Langenberg D.M., de Waal Malefyt R., Ottenhoff T.H., et al. Divergent effects of IL-12 and IL-23 on the production of IL-17 by human T cells. European Journal of Immunology 2006, 36:661-670.
61. Zhou L., Ivanov I.I., Spolski R., Min R., Shenderov K., Egawa T., et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nature Immunology 2007, 8:967-974.
62. Nurieva R., Yang X.O., Martinez G., Zhang Y., Panopoulos A.D., Ma L., et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 2007, 448:480-483.
63. Korn T., Bettelli E., Gao W., Awasthi A., Jäger A., Strom T.B., et al. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 2007, 448:484-487.
64. 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. Journal of Immunology 2007, 178:732-739.
65. Li Y., Yee C. IL-21 mediated Foxp3 suppression leads to enhanced generation of antigen-specific CD8+ cytotoxic T lymphocytes. Blood 2008, 111:229-235.
66. Attridge K., Wang C.J., Wardzinski L., Kenefeck R., Chamberlain J.L., Manzotti C., et al. IL-21 inhibits T cell IL-2 production and impairs Treg homeostasis. Blood 2012, 119:4656-4664.
67. Hong J.J., Amancha P.K., Rogers K., Ansari A.A., Villinger F. Spatial alterations between CD4+ T follicular helper, B, and CD8+ T cells during simian immunodeficiency virus infection: T/B cell homeostasis, activation, and potential mechanism for viral escape. Journal of Immunology 2012, 188:3247-3256.
68. Dandekar S., George M.D., Baumler A.J. Th17 cells HIV and the gut mucosal barrier. Current Opinion in HIV and AIDS 2010, 5:173-178.
69. Hunt P.W. Th17, gut, and HIV: therapeutic implications. Current Opinion in HIV and AIDS 2010, 5:189-193.
70. Brenchley J.M., Paiardini M., Knox K.S., Asher A.I., Cervasi B., Asher T.E., et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood 2008, 112:2826-2835.
71. Favre D., Lederer S., Kanwar B., Ma Z.M., Proll S., Kasakow Z., et al. Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. PLoS Pathogens 2009, 5:e1000295.
72. Cecchinato V., Franchini G. Th17 cells in pathogenic simian immunodeficiency virus infection of macaques. Current Opinion in HIV and AIDS 2010, 5:141-145.
73. Ciccone E.J., Greenwald J.H., Lee P.I., Biancotto A., Read S.W., Yao M.A., et al. CD4+ T cells, including Th17 and cycling subsets, are intact in the gut mucosa of HIV-1-infected long-term nonprogressors. Journal of Virology 2011, 85:5880-5888.
74. Demberg T., Ettinger A.C., Aladi S., McKinnon K., Kuddo T., Venzon D., et al. Strong viremia control in vaccinated macaques does not prevent gradual Th17 cell loss from central memory. Vaccine 2011, 29:6017-6028.
75. Cecchinato V., Trindade C.J., Laurence A., Heraud J.M., Brenchley J.M., Ferrari M.G., et al. Altered balance between Th17 and Th1 cells at mucosal sites predicts AIDS progression in simian immunodeficiency virus-infected macaques. Mucosal Immunology 2008, 1:279-288.
76. Kagi D., Ledermann B., Burki K., Seiler P., Odermatt B., Olsen K.J., et al. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature 1994, 369:31-37.
77. Balkow S., Kersten A., Tran T.T., Stehle T., Grosse P., Museteanu C., et al. Concerted action of the FasL/Fas and perforin/granzyme A and B pathways is mandatory for the development of early viral hepatitis but not for recovery from viral infection. Journal of Virology 2001, 75:8781-8791.
78. Smith-Garvin J.E., Burns J.C., Gohil M., Zou T., Kim J.S., Maltzman J.S., et al. T-cell receptor signals direct the composition and function of the memory CD8+ T-cell pool. Blood 2010, 116:5548-5559.
79. Wiehagen K.R., Corbo E., Schmidt M., Shin H., Wherry E.J., Maltzman J.S. Loss of tonic T-cell receptor signals alters the generation but not the persistence of CD8+ memory T cells. Blood 2010, 116:5560-5570.
80. Rudd C.E., Taylor A., Schneider H. CD28 and CTLA-4 coreceptor expression and signal transduction. Immunological Reviews 2009, 229:12-26.
81. Curtsinger J.M., Schmidt C.S., Mondino A., Lins D.C., Kedl R.M., Jenkins M.K., et al. Inflammatory cytokines provide a third signal for activation of naive CD4+ and CD8+ T cells. Journal of Immunology 1999, 162:3256-3262.
82. Curtsinger J.M., Valenzuela J.O., Agarwal P., Lins D., Mescher M.F. Type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation. Journal of Immunology 2005, 174:4465-4469.
83. Zeng R., Spolski R., Finkelstein S.E., Oh S., Kovanen P.E., Hinrichs C.S., et al. Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function. Journal of Experimental Medicine 2005, 201:139-148.
84. Parmigiani A., Pallin M.F., Schmidtmayerova H., Lichtenheld M.G., Pahwa S. Interleukin-21 and cellular activation concurrently induce potent cytotoxic function and promote antiviral activity in human CD8 T cells. Human Immunology 2011, 72:115-123.
85. Hogg A.E., Bowick G.C., Herzog N.K., Cloyd M.W., Endsley J.J. Induction of granulysin in CD8+ T cells by IL-21 and IL-15 is suppressed by human immunodeficiency virus-1. Journal of Leukocyte Biology 2009, 86:1191-1203.
86. Kaka A.S., Shaffer D.R., Hartmaier R., Leen A.M., Lu A., Bear A., et al. Genetic modification of T cells with IL-21 enhances antigen presentation and generation of central memory tumor-specific cytotoxic T-lymphocytes. Journal of Immunotherapy 2009, 32:726-736.
87. Alves N.L., Arosa F.A., van Lier R.A. IL-21 sustains CD28 expression on IL-15-activated human naive CD8+ T cells. Journal of Immunology 2005, 175:755-762.
88. Chen Y.H., Kuo M.L., Cheng P.J., Hsaio H.S., Lee P.T., Lin S.J. Regulation of CD28 expression on umbilical cord blood and adult peripheral blood CD8+ T cells by interleukin (IL)-15/IL-21. Cytokine 2012, 58:40-46.
89. Allard E.L., Hardy M.P., Leignadier J., Marquis M., Rooney J., Lehoux D., et al. Overexpression of IL-21 promotes massive CD8+ memory T cell accumulation. European Journal of Immunology 2007, 37:3069-3077.
90. Cui W., Liu Y., Weinstein J.S., Craft J., Kaech S.M. An interleukin-21-interleukin-10-STAT3 pathway is critical for functional maturation of memory CD8+ T cells. Immunity 2011, 35:792-805.
91. Siegel A.M., Heimall J., Freeman A.F., Hsu A.P., Brittain E., Brenchley J.M., et al. A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory. Immunity 2011, 35:806-818.
92. Novy P., Huang X., Leonard W.J., Yang Y. Intrinsic IL-21 signaling is critical for CD8 T cell survival and memory formation in response to vaccinia viral infection. Journal of Immunology 2011, 186:2729-2738.
93. Hersperger A.R., Pereyra F., Nason M., Demers K., Sheth P., Shin L.Y., et al. Perforin expression directly ex vivo by HIV-specific CD8 T-cells is a correlate of HIV elite control. PLoS Pathogens 2010, 6:e1000917.
94. Migueles S.A., Osborne C.M., Royce C., Compton A.A., Joshi R.P., Weeks K.A., et al. Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. Immunity 2008, 29:1009-1021.
95. Schmitz J.E., Kuroda M.J., Santra S., Sasseville V.G., Simon M.A., Lifton M.A., et al. Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 1999, 283:857-860.
96. Alter G., Altfeld M. NK cells in HIV-1 infection: evidence for their role in the control of HIV-1 infection. Journal of Internal Medicine 2009, 265:29-42.
97. Tiemessen C.T., Shalekoff S., Meddows-Taylor S., Schramm D.B., Papathanasopoulos M.A., Gray G.E., et al. Natural killer cells that respond to human immunodeficiency virus type 1 (HIV-1) peptides are associated with control of HIV-1 infection. Journal of Infectious Diseases 2010, 202:1444-1453.
98. Champagne P., Ogg G.S., King A.S., Knabenhans C., Ellefsen K., Nobile M., et al. Skewed maturation of memory HIV-specific CD8 T lymphocytes. Nature 2001, 410:106-111.
99. 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. Journal of Virology 2007, 81:10861-10868.
100. White L., Krishnan S., Strbo N., Liu H., Kolber M.A., Lichtenheld M.G., et al. Differential effects of IL-21 and IL-15 on perforin expression, lysosomal degranulation, and proliferation in CD8 T cells of patients with human immunodeficiency virus-1 (HIV). Blood 2007, 109:3873-3880.
101. Iannello A., Boulassel M.R., Samarani S., Tremblay C., Toma E., Routy J.P., et al. IL-21 enhances NK cell functions and survival in healthy and HIV-infected patients with minimal stimulation of viral replication. Journal of Leukocyte Biology 2010, 87:857-867.
102. Krensky A.M., Clayberger C. Biology and clinical relevance of granulysin. Tissue Antigens 2009, 73:193-198.
103. Mehta D.S., Wurster A.L., Whitters M.J., Young D.A., Collins M., Grusby M.J. IL-21 induces the apoptosis of resting and activated primary B cells. Journal of Immunology 2003, 170:4111-4118.
104. Recher M., Berglund L.J., Avery D.T., Cowan M.J., Gennery A.R., Smart J., et al. IL-21 is the primary common gamma chain-binding cytokine required for human B-cell differentiation in vivo. Blood 2011, 118:6824-6835.
105. Rankin A.L., MacLeod H., Keegan S., Andreyeva T., Lowe L., Bloom L., et al. IL-21 receptor is critical for the development of memory B cell responses. Journal of Immunology 2011, 186:667-674.
106. Avery D.T., Deenick E.K., Ma C.S., Suryani S., Simpson N., Chew G.Y., et al. B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans. Journal of Experimental Medicine 2010, 207:155-171.
107. Kurosaki T., Shinohara H., Baba Y. B cell signaling and fate decision. Annual Review of Immunology 2010, 28:21-55.
108. Bryant V.L., Ma C.S., Avery D.T., Li Y., Good K.L., Corcoran L.M., et al. Cytokine-mediated regulation of human B cell differentiation into Ig-secreting cells: predominant role of IL-21 produced by CXCR5+ T follicular helper cells. Journal of Immunology 2007, 179:8180-8190.
109. Zotos D., Coquet J.M., Zhang Y., Light A., D'Costa K., Kallies A., et al. IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism. Journal of Experimental Medicine 2010, 207:365-378.
110. Diehl S.A., Schmidlin H., Nagasawa M., van Haren S.D., Kwakkenbos M.J., Yasuda E., et al. STAT3-mediated up-regulation of BLIMP1 Is coordinated with BCL6 down-regulation to control human plasma cell differentiation. Journal of Immunology 2008, 180:4805-4815.
111. Johnston R.J., Poholek A.C., DiToro D., Yusuf I., Eto D., Barnett B., et al. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 2009, 325:1006-1010.
112. Linterman M.A., Beaton L., Yu D., Ramiscal R.R., Srivastava M., Hogan J.J., et al. IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses. Journal of Experimental Medicine 2010, 207:353-363.
113. Moir S., Fauci A.S. B cells in HIV infection and disease. Nature Reviews Immunology 2009, 9:235-245.
114. van Grevenynghe J., Cubas R.A., Noto A., DaFonseca S., He Z., Peretz Y., et al. Loss of memory B cells during chronic HIV infection is driven by Foxo3a- and TRAIL-mediated apoptosis. Journal of Clinical Investigation 2011, 121:3877-3888.
115. Malaspina A., Moir S., Orsega S.M., Vasquez J., Miller N.J., Donoghue E.T., et al. Compromised B cell responses to influenza vaccination in HIV-infected individuals. Journal of Infectious Diseases 2005, 191:1442-1450.
116. Moir S., Malaspina A., Ho J., Wang W., Dipoto A.C., O'Shea M.A., et al. Normalization of B cell counts and subpopulations after antiretroviral therapy in chronic HIV disease. Journal of Infectious Diseases 2008, 197:572-579.
117. Pallikkuth S., Rogers K., Villinger F., Dosterii M., Vaccari M., Franchini G., et al. Interleukin-21 administration to rhesus macaques chronically infected with simian immunodeficiency virus increases cytotoxic effector molecules in T cells and NK cells and enhances B cell function without increasing immune activation or viral replication. Vaccine 2011, 29:9229-9238.
118. Pallikkuth S., Pilakka Kanthikeel S., Silva S.Y., Fischl M., Pahwa R., Pahwa S. Upregulation of IL-21 receptor on B cells and IL-21 secretion distinguishes novel 2009 H1N1 vaccine responders from nonresponders among HIV-infected persons on combination antiretroviral therapy. Journal of Immunology 2011, 186:6173-6181.
119. Pallikkuth S., Kanthikeel S.P., Silva S.Y., Fischl M., Pahwa R., Pahwa S. Innate immune defects correlate with failure of antibody responses to H1N1/09 vaccine in HIV-infected patients. Journal of Allergy and Clinical Immunology 2011, 128:1279-1285.
120. Avery D.T., Bryant V.L., Ma C.S., de Waal Malefyt R., Tangye S.G. IL-21-induced isotype switching to IgG and IgA by human naive B cells is differentially regulated by IL-4. Journal of Immunology 2008, 181:1767-1779.
121. Borte S., Pan-Hammarstrom Q., Liu C., Sack U., Borte M., Wagner U., et al. Interleukin-21 restores immunoglobulin production ex vivo in patients with common variable immunodeficiency and selective IgA deficiency. Blood 2009, 114:4089-4098.
122. Konforte D., Simard N., Paige C.J. IL-21: an executor of B cell fate. Journal of Immunology 2009, 182:1781-1787.
123. Strbo N., de Armas L., Liu H., Kolber M.A., Lichtenheld M., Pahwa S. IL-21 augments natural killer effector functions in chronically HIV-infected individuals. AIDS 2008, 22:1551-1560.
124. Beq S., Nugeyre M.T., Ho Tsong Fang R., Gautier D., Legrand R., Schmitt N., et al. IL-7 induces immunological improvement in SIV-infected rhesus macaques under antiviral therapy. Journal of Immunology 2006, 176:914-922.
125. Fry T.J., Moniuszko M., Creekmore S., Donohue S.J., Douek D.C., Giardina S., et al. IL-7 therapy dramatically alters peripheral T-cell homeostasis in normal and SIV-infected nonhuman primates. Blood 2003, 101:2294-2299.
126. Moniuszko M., Edghill-Smith Y., Venzon D., Stevceva L., Nacsa J., Tryniszewska E., et al. Decreased number of CD4+ and CD8+ T cells that express the interleukin-7 receptor in blood and tissues of SIV-infected macaques. Virology 2006, 356:188-197.
127. Craiu A., Barouch D.H., Zheng X.X., Kuroda M.J., Schmitz J.E., Lifton M.A., et al. An IL-2/Ig fusion protein influences CD4+ T lymphocytes in naive and simian immunodeficiency virus-infected Rhesus monkeys. AIDS Research and Human Retroviruses 2001, 17:873-886.
128. Villinger F., Miller R., Mori K., Mayne A.E., Bostik P., Sundstrom J.B., et al. IL-15 is superior to IL-2 in the generation of long-lived antigen specific memory CD4 and CD8 T cells in rhesus macaques. Vaccine 2004, 22:3510-3521.
129. 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. Journal of Virology 2005, 79:4877-4885.
130. 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. Journal of Clinical Investigation 2006, 116:1514-1524.
131. 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. Journal of Immunology 2008, 180:350-360.
132. Villinger F., Bucur S., Chikkala N.F., Brar S.S., Bostik P., Mayne A.E., et al. In vitro and in vivo responses to interleukin 12 are maintained until the late SIV infection stage but lost during AIDS. AIDS Research and Human Retroviruses 2000, 16:751-763.
133. Watanabe N., Sypek J.P., Mittler S., Reimann K.A., Flores-Villanueva P., Voss G., et al. Administration of recombinant human interleukin 12 to chronically SIVmac-infected rhesus monkeys. AIDS Research and Human Retroviruses 1998, 14:393-399.