IL-21 optimizes T cell and humoral responses in the central nervous system during viral encephalitis

Journal of Neuroimmunology

Volumn 263, Issue 1-2, 2013, Pages 43-54

  Phares, Timothy W ^a   DiSano, Krista D ^a,b   Hinton, David R ^c   Hwang, Mihyun ^a   Zajac, Allan J ^d   Stohlman, Stephen A ^a   Bergmann, Cornelia C ^a  

^a LERNER RESEARCH INSTITUTE   (United States)

^b KENT STATE UNIVERSITY   (United States)

^c UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^d University of Alabama at Birmingham   (United States)

Author keywords

CD4+ and CD8+ T cells; Central nervous system; Inflammation; Interleukin; Neuroimmunology

Indexed keywords

GAMMA INTERFERON; GRANZYME B; HERMES ANTIGEN; INTERLEUKIN 10; INTERLEUKIN 2; INTERLEUKIN 21; INTERLEUKIN 21 RECEPTOR; L SELECTIN; MESSENGER RNA; RANTES; TRANSCRIPTION FACTOR FOXP3;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIVIRAL ACTIVITY; ARTICLE; B LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL EXPANSION; CELL SPECIFICITY; CELL SURVIVAL; CELLULAR IMMUNITY; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; CYTOKINE RELEASE; EFFECTOR CELL; HUMORAL IMMUNITY; IMMUNOPATHOGENESIS; KINETICS; LYMPHOCYTE ACTIVATION; MORBIDITY; MORTALITY; MOUSE; NONHUMAN; PERSISTENT VIRUS INFECTION; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION; TRANSCRIPTION REGULATION; UPREGULATION; VIRUS ENCEPHALITIS; VIRUS INHIBITION;

CD4(+) AND CD8(+) T CELLS; CENTRAL NERVOUS SYSTEM; INFLAMMATION; INTERLEUKIN; NEUROIMMUNOLOGY;

ANIMALS; B-LYMPHOCYTE SUBSETS; CENTRAL NERVOUS SYSTEM; CORONAVIRUS; CORONAVIRUS INFECTIONS; ENCEPHALITIS, VIRAL; IMMUNITY, HUMORAL; INTERLEUKINS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; T-LYMPHOCYTE SUBSETS; VIRUS REPLICATION;

EID: 84884821531     PISSN: 01655728     EISSN: 18728421     Source Type: Journal    
DOI: 10.1016/j.jneuroim.2013.07.019     Document Type: Article

References (65)

1. Barker B.R., Gladstone M.N., Gillard G.O., Panas M.W., Letvin N.L. Critical role for IL-21 in both primary and memory anti-viral CD8(+) T-cell responses. Eur. J. Immunol. 2010, 40:3085-3096.
2. Bergmann C.C., Altman J.D., Hinton D., Stohlman S.A. Inverted immunodominance and impaired cytolytic function of CD8+ T cells during viral persistence in the central nervous system. J. Immunol. 1999, 163:3379-3387.
3. Bergmann C.C., Parra B., Hinton D.R., Ramakrishna C., Dowdell K.C., Stohlman S.A. Perforin and gamma interferon-mediated control of coronavirus central nervous system infection by CD8 T cells in the absence of CD4 T cells. J. Virol. 2004, 78:1739-1750.
4. Bergmann C.C., Lane T.E., Stohlman S.A. Coronavirus infection of the central nervous system: host-virus stand-off. Nat. Rev. Microbiol. 2006, 4:121-132.
5. Bessa J., Kopf M., Bachmann M.F. Cutting edge: IL-21 and TLR signaling regulate germinal center responses in a B cell-intrinsic manner. J. Immunol. 2010, 184:4615-4619.
6. Brandt K., Bulfone-Paus S., Foster D.C., Ruckert R. Interleukin-21 inhibits dendritic cell activation and maturation. Blood 2003, 102:4090-4098.
7. 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. J. Invest. Dermatol. 2003, 121:1379-1382.
8. Casey K.A., Mescher M.F. IL-21 promotes differentiation of naive CD8 T cells to a unique effector phenotype. J. Immunol. 2007, 178:7640-7648.
9. Dorfmeier C.L., Tzvetkov E.P., Gatt A., Mcgettigan J.P. Investigating the role for IL-21 in rabies virus vaccine-induced immunity. PLoS Negl. Trop. Dis. 2013, 7:e2129.
10. Elsaesser H., Sauer K., Brooks D.G. IL-21 is required to control chronic viral infection. Science 2009, 324:1569-1572.
11. Fleming J.O., Trousdale M.D., El-Zaatari F.A., Stohlman S.A., Weiner L.P. Pathogenicity of antigenic variants of murine coronavirus JHM selected with monoclonal antibodies. J. Virol. 1986, 58:869-875.
12. Frohlich A., Kisielow J., Schmitz I., Freigang S., Shamshiev A.T., Weber J., Marsland B.J., Oxenius A., Kopf M. IL-21R on T cells is critical for sustained functionality and control of chronic viral infection. Science 2009, 324:1576-1580.
13. Gonzalez J.M., Bergmann C.C., Ramakrishna C., Hinton D.R., Atkinson R., Hoskin J., Macklin W.B., Stohlman S.A. Inhibition of interferon-gamma signaling in oligodendroglia delays coronavirus clearance without altering demyelination. Am. J. Pathol. 2006, 168:796-804.
14. Hamo L., Stohlman S.A., Otto-Duessel M., Bergmann C.C. Distinct regulation of MHC molecule expression on astrocytes and microglia during viral encephalomyelitis. Glia 2007, 55:1169-1177.
15. Ireland D.D., Stohlman S.A., Hinton D.R., Kapil P., Silverman R.H., Atkinson R.A., Bergmann C.C. RNase L mediated protection from virus induced demyelination. PLoS Pathog. 2009, 5:e1000602.
16. Kapil P., Atkinson R., Ramakrishna C., Cua D.J., Bergmann C.C., Stohlman S.A. Interleukin-12 (IL-12), but not IL-23, deficiency ameliorates viral encephalitis without affecting viral control. J. Virol. 2009, 83:5978-5986.
17. King I.L., Mohrs K., Mohrs M. A nonredundant role for IL-21 receptor signaling in plasma cell differentiation and protective type 2 immunity against gastrointestinal helminth infection. J. Immunol. 2010, 185:6138-6145.
18. Lin M.T., Stohlman S.A., Hinton D.R. Mouse hepatitis virus is cleared from the central nervous systems of mice lacking perforin-mediated cytolysis. J. Virol. 1997, 71:383-391.
19. Lin M.T., Hinton D.R., Marten N.W., Bergmann C.C., Stohlman S.A. Antibody prevents virus reactivation within the central nervous system. J. Immunol. 1999, 162:7358-7368.
20. Linterman M.A., Beaton L., Yu D., Ramiscal R.R., Srivastava M., Hogan J.J., Verma N.K., Smyth M.J., Rigby R.J., Vinuesa C.G. IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses. J. Exp. Med. 2010, 207:353-363.
21. Liu R., Bai Y., Vollmer T.L., Bai X.F., Jee Y., Tang Y.Y., Campagnolo D.I., Collins M., Young D.A., La Cava A., Shi F.D. IL-21 receptor expression determines the temporal phases of experimental autoimmune encephalomyelitis. Exp. Neurol. 2008, 211:14-24.
22. Malone K.E., Stohlman S.A., Ramakrishna C., Macklin W., Bergmann C.C. Induction of class I antigen processing components in oligodendroglia and microglia during viral encephalomyelitis. Glia 2008, 56:426-435.
23. Marques C.P., Kapil P., Hinton D.R., Hindinger C., Nutt S.L., Ransohoff R.M., Phares T.W., Stohlman S.A., Bergmann C.C. CXCR3-dependent plasma blast migration to the central nervous system during viral encephalomyelitis. J. Virol. 2011, 85:6136-6147.
24. Marten N.W., Stohlman S.A., Zhou J., Bergmann C.C. Kinetics of virus-specific CD8+-T-cell expansion and trafficking following central nervous system infection. J. Virol. 2003, 77:2775-2778.
25. Melief C.J., Schoenberger S.P. Enhancement of proliferation and downregulation of TRAIL expression on CD8+ T cells by IL-21. Eur. J. Immunol. 2010, 40:2990-2992.
26. Nohra R., Beyeen A.D., Guo J.P., Khademi M., Sundqvist E., Hedreul M.T., Sellebjerg F., Smestad C., Oturai A.B., Harbo H.F., Wallstrom E., Hillert J., Alfredsson L., Kockum I., Jagodic M., Lorentzen J., Olsson T. RGMA and IL21R show association with experimental inflammation and multiple sclerosis. Genes Immun. 2010, 11:279-293.
27. 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. J. Immunol. 2011, 186:2729-2738.
28. Nurieva R., Yang X.O., Martinez G., Zhang Y., Panopoulos A.D., Ma L., Schluns K., Tian Q., Watowich S.S., Jetten A.M., Dong C. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 2007, 448:480-483.
29. Ostiguy V., Allard E.L., Marquis M., Leignadier J., Labrecque N. IL-21 promotes T lymphocyte survival by activating the phosphatidylinositol-3 kinase signaling cascade. J. Leukoc. Biol. 2007, 82:645-656.
30. Ozaki K., Spolski R., Feng C.G., Qi C.F., Cheng J., Sher A., Morse H.C., Liu C., Schwartzberg P.L., Leonard W.J. A critical role for IL-21 in regulating immunoglobulin production. Science 2002, 298:1630-1634.
31. Pallikkuth S., Parmigiani A., Pahwa S. The role of interleukin-21 in HIV infection. Cytokine Growth Factor Rev. 2012, 23:173-180.
32. Parra B., Hinton D.R., Marten N.W., Bergmann C.C., Lin M.T., Yang C.S., Stohlman S.A. IFN-gamma is required for viral clearance from central nervous system oligodendroglia. J. Immunol. 1999, 162:1641-1647.
33. Pearce E.L., Mullen A.C., Martins G.A., Krawczyk C.M., Hutchins A.S., Zediak V.P., Banica M., Dicioccio C.B., Gross D.A., Mao C.A., Shen H., Cereb N., Yang S.Y., Lindsten T., Rossant J., Hunter C.A., Reiner S.L. Control of effector CD8+ T cell function by the transcription factor Eomesodermin. Science 2003, 302:1041-1043.
34. Phares T.W., Ramakrishna C., Parra G.I., Epstein A., Chen L., Atkinson R., Stohlman S.A., Bergmann C.C. Target-dependent B7-H1 regulation contributes to clearance of central nervous system infection and dampens morbidity. J. Immunol. 2009, 182:5430-5438.
35. Phares T.W., Stohlman S.A., Hinton D.R., Atkinson R., Bergmann C.C. Enhanced antiviral T cell function in the absence of B7-H1 is insufficient to prevent persistence but exacerbates axonal bystander damage during viral encephalomyelitis. J. Immunol. 2010, 185:5607-5618.
36. Phares T.W., Marques C.P., Stohlman S.A., Hinton D.R., Bergmann C.C. Factors supporting intrathecal humoral responses following viral encephalomyelitis. J. Virol. 2011, 85:2589-2598.
37. Phares T.W., Stohlman S.A., Hinton D.R., Bergmann C.C. Enhanced CD8 T-cell anti-viral function and clinical disease in B7-H1-deficient mice requires CD4 T cells during encephalomyelitis. J. Neuroinflammation 2012, 9:269.
38. Phares T.W., Stohlman S.A., Hwang M., Min B., Hinton D.R., Bergmann C.C. CD4 T cells promote CD8 T cell immunity at the priming and effector site during viral encephalitis. J. Virol. 2012, 86:2416-2427.
39. Piao W.H., Jee Y.H., Liu R.L., Coons S.W., Kala M., Collins M., Young D.A., Campagnolo D.I., Vollmer T.L., Bai X.F., La Cava A., Shi F.D. IL-21 modulates CD4+ CD25+ regulatory T-cell homeostasis in experimental autoimmune encephalomyelitis. Scand. J. Immunol. 2008, 67:37-46.
40. Puntambekar S.S., Bergmann C.C., Savarin C., Karp C.L., Phares T.W., Parra G.I., Hinton D.R., Stohlman S.A. Shifting hierarchies of interleukin-10-producing T cell populations in the central nervous system during acute and persistent viral encephalomyelitis. J. Virol. 2011, 85:6702-6713.
41. Ramakrishna C., Stohlman S.A., Atkinson R.D., Shlomchik M.J., Bergmann C.C. Mechanisms of central nervous system viral persistence: the critical role of antibody and B cells. J. Immunol. 2002, 168:1204-1211.
42. Ramakrishna C., Bergmann C.C., Atkinson R., Stohlman S.A. Control of central nervous system viral persistence by neutralizing antibody. J. Virol. 2003, 77:4670-4678.
43. Rankin A.L., Macleod H., Keegan S., Andreyeva T., Lowe L., Bloom L., Collins M., Nickerson-Nutter C., Young D., Guay H. IL-21 receptor is critical for the development of memory B cell responses. J. Immunol. 2011, 186:667-674.
44. Rasheed M.A., Latner D.R., Aubert R.D., Gourley T., Spolski R., Davis C.W., Langley W.A., Ha S.J., Ye L., Sarkar S., Kalia V., Konieczny B.T., Leonard W.J., Ahmed R. IL-21 is a critical cytokine for the generation of virus-specific long-lived plasma cells. J. Virol. 2013, 87:7737-7746.
45. 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.
46. Savarin C., Stohlman S.A., Atkinson R., Ransohoff R.M., Bergmann C.C. Monocytes regulate T cell migration through the glia limitans during acute viral encephalitis. J. Virol. 2010, 84:4878-4888.
47. Spolski R., Wang L., Wan C.K., Bonville C.A., Domachowske J.B., Kim H.P., Yu Z., Leonard W.J. IL-21 promotes the pathologic immune response to pneumovirus infection. J. Immunol. 2012, 188:1924-1932.
48. Strengell M., Lehtonen A., Matikainen S., Julkunen I. IL-21 enhances SOCS gene expression and inhibits LPS-induced cytokine production in human monocyte-derived dendritic cells. J. Leukoc. Biol. 2006, 79:1279-1285.
49. Stumhofer J.S., Silver J.S., Hunter C.A. IL-21 Is Required for Optimal Antibody Production and T Cell Responses during Chronic Toxoplasma gondii Infection. PLoS One 2013, 8:e62889.
50. Sullivan B.M., Juedes A., Szabo S.J., Von Herrath M., Glimcher L.H. Antigen-driven effector CD8 T cell function regulated by T-bet. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:15818-15823.
51. Sutherland A.P., Joller N., Michaud M., Liu S.M., Kuchroo V.K., Grusby M.J. IL-21 promotes CD8+ CTL activity via the transcription factor T-bet. J. Immunol. 2013, 190:3977-3984.
52. Szabo S.J., Sullivan B.M., Stemmann C., Satoskar A.R., Sleckman B.P., Glimcher L.H. Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science 2002, 295:338-342.
53. Trandem K., Zhao J., Fleming E., Perlman S. Highly activated cytotoxic CD8 T cells express protective IL-10 at the peak of coronavirus-induced encephalitis. J. Immunol. 2011, 186:3642-3652.
54. Tschen S.I., Bergmann C.C., Ramakrishna C., Morales S., Atkinson R., Stohlman S.A. Recruitment kinetics and composition of antibody-secreting cells within the central nervous system following viral encephalomyelitis. J. Immunol. 2002, 168:2922-2929.
55. Tschen S.I., Stohlman S.A., Ramakrishna C., Hinton D.R., Atkinson R.D., Bergmann C.C. CNS viral infection diverts homing of antibody-secreting cells from lymphoid organs to the CNS. Eur. J. Immunol. 2006, 36:603-612.
56. Tzartos J.S., Craner M.J., Friese M.A., Jakobsen K.B., Newcombe J., Esiri M.M., Fugger L. IL-21 and IL-21 receptor expression in lymphocytes and neurons in multiple sclerosis brain. Am. J. Pathol. 2011, 178:794-802.
57. Vollmer T.L., Liu R., Price M., Rhodes S., La Cava A., Shi F.D. Differential effects of IL-21 during initiation and progression of autoimmunity against neuroantigen. J. Immunol. 2005, 174:2696-2701.
58. Weiss S.R., Leibowitz J.L. Coronavirus pathogenesis. Adv. Virus Res. 2011, 81:85-164.
59. Wu A., Zhong X., Wang H., Xu W., Cheng C., Dai Y., Bao J., Qiu W., Lu Z., Hu X. Cerebrospinal fluid IL-21 levels in neuromyelitis optica and multiple sclerosis. Can. J. Neurol. Sci. 2012, 39:813-820.
60. 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.
61. Yi J.S., Cox M.A., Zajac A.J. Interleukin-21: a multifunctional regulator of immunity to infections. Microbes Infect. 2010, 12:1111-1119.
62. 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. J. Immunol. 2010, 185:4835-4845.
63. Zeng R., Spolski R., Finkelstein S.E., Oh S., Kovanen P.E., Hinrichs C.S., Pise-Masison C.A., Radonovich M.F., Brady J.N., Restifo N.P., Berzofsky J.A., Leonard W.J. Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function. J. Exp. Med. 2005, 201:139-148.
64. Zhou J., Hinton D.R., Stohlman S.A., Liu C.P., Zhong L., Marten N.W. Maintenance of CD8+ T cells during acute viral infection of the central nervous system requires CD4+ T cells but not interleukin-2. Viral Immunol. 2005, 18:162-169.
65. Zotos D., Coquet J.M., Zhang Y., Light A., D'costa K., Kallies A., Corcoran L.M., Godfrey D.I., Toellner K.M., Smyth M.J., Nutt S.L., Tarlinton D.M. IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism. J. Exp. Med. 2010, 207:365-378.