Latent virus infection upregulates CD40 expression facilitating enhanced autoimmunity in a model of multiple sclerosis

Scientific Reports

Volumn 5, Issue , 2015, Pages

  Casiraghi, Costanza ^a,b   Márquez, Ana Citlali ^a   Shanina, Iryna ^a   Horwitz, Marc Steven ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CD40 ANTIGEN; STAT1 PROTEIN;

ANIMAL; ANTIGEN PRESENTING CELL; AUTOIMMUNITY; BRAIN; COMPLICATION; DISEASE MODEL; EPSTEIN BARR VIRUS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; GENE EXPRESSION; GENETICS; HERPES VIRUS INFECTION; HUMAN; IMMUNOLOGY; IMMUNOPHENOTYPING; METABOLISM; MOUSE; MULTIPLE SCLEROSIS; PATHOLOGY; PHENOTYPE; PHYSIOLOGY; RHADINOVIRUS; T LYMPHOCYTE SUBPOPULATION; UPREGULATION; VIROLOGY; VIRUS LATENCY;

ANIMALS; ANTIGEN-PRESENTING CELLS; ANTIGENS, CD40; AUTOIMMUNITY; BRAIN; DISEASE MODELS, ANIMAL; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; GENE EXPRESSION; HERPESVIRIDAE INFECTIONS; HERPESVIRUS 4, HUMAN; HUMANS; IMMUNOPHENOTYPING; MICE; MULTIPLE SCLEROSIS; PHENOTYPE; RHADINOVIRUS; STAT1 TRANSCRIPTION FACTOR; T-LYMPHOCYTE SUBSETS; UP-REGULATION; VIRUS LATENCY;

EID: 84941585334     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep13995     Document Type: Article

References (59)

1. Niller H. H., Wolf H., & Minarovits J. Regulation, and dysregulation of Epstein-Barr virus latency: implications for the development of autoimmune diseases. Autoimmunity 41, 298-328, (2008
2. Pender M. P. Infection of autoreactive B lymphocytes with EBV, causing chronic autoimmune diseases. Trends Immunol 24, 584-588 (2003
3. Posnett D. N. Herpesviruses, and autoimmunity. Curr Opin Investig Drugs 9, 505-514 (2008
4. Berner B. R., et al. Phenotypic, and functional analysis of EBV-specific memory CD8 cells in SLE. Cell Immunol 235, 29-38 (2005
5. Jilek S., et al. Strong EBV-specific CD8+ T-cell response in patients with early multiple sclerosis. Brain 131, 1712-1721 (2008
6. Kang I., et al. Defective control of latent Epstein-Barr virus infection in systemic lupus erythematosus. J Immunol 172, 1287-1294 (2004
7. Larsen M., et al. Exhausted cytotoxic control of Epstein-Barr virus in human lupus. PLoS Pathog 7, e1002328 (2011
8. Levin L. I., et al. Temporal relationship between elevation of epstein-barr virus antibody titers, and initial onset of neurological symptoms in multiple sclerosis. JAMA 293, 2496-2500 (2005
9. Lunemann J. D., et al. Increased frequency, and broadened specificity of latent EBV nuclear antigen-1-specific T cells in multiple sclerosis. Brain 129, 1493-1506 (2006
10. Lunemann J. D., et al. EBNA1-specific T cells from patients with multiple sclerosis cross react with myelin antigens, and coproduce IFN-gamma, and IL-2. J Exp Med 205, 1763-1773 (2008
11. Pender M. P., Csurhes P. A., Pfluger C. M., & Burrows S. R. CD8 T cell deficiency impairs control of Epstein-Barr virus, and worsens with age in multiple sclerosis. J Neurol Neurosurg Psychiatry 83, 353-354 (2011
12. McClain M. T., et al. Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry. Nat Med 11, 85-89 (2005
13. Ascherio A., & Munger K. L. Environmental risk factors for multiple sclerosis. Part I: the role of infection. Ann Neurol 61, 288-299 (2007
14. James J. A., et al. Systemic lupus erythematosus in adults is associated with previous Epstein-Barr virus exposure. Arthritis Rheum 44, 1122-1126 (2001
15. Sargsyan S. A., et al. Absence of Epstein-Barr virus in the brain, and CSF of patients with multiple sclerosis. Neurology 74, 1127-1135 (2010
16. Serafini B., et al. Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain. J Exp Med 204, 2899-2912 (2007
17. Willis S. N., et al. Epstein-Barr virus infection is not a characteristic feature of multiple sclerosis brain. Brain 132, 3318-3328 (2009
18. Olivadoti M., Toth L. A., Weinberg J., & Opp M. R. Murine gammaherpesvirus 68: a model for the study of Epstein-Barr virus infections, and related diseases. Comp Med 57, 44-50 (2007
19. Flano E., Woodland D. L., & Blackman M. A. A mouse model for infectious mononucleosis. Immunol Res 25, 201-217 (2002
20. Peacock J. W., Elsawa S. F., Petty C. C., Hickey W. F., & Bost K. L. Exacerbation of experimental autoimmune encephalomyelitis in rodents infected with murine gammaherpesvirus-68. Eur J Immunol 33, 1849-1858 (2003
21. Nelson D. A., Petty C. C., & Bost K. L. Infection with murine gammaherpesvirus 68 exacerbates inflammatory bowel disease in IL-10-deficient mice. Inflamm Res 58, 881-889 (2009
22. Cadwell K., et al. Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine. Cell 141, 1135-1145 (2010
23. Casiraghi C., et al. Gammaherpesvirus latency accentuates EAE pathogenesis: relevance to Epstein-Barr virus, and multiple sclerosis. PLoS Pathog 8, e1002715 (2012
24. Ma D. Y., & Clark E. A. The role of CD40, and CD154/CD40L in dendritic cells. Semin Immunol 21, 265-272 (2009
25. Harnett M. M. CD40: a growing cytoplasmic tale. Sci STKE 2004, pe25 (2004
26. Hart D. N., & McKenzie J. L. Isolation, and characterization of human tonsil dendritic cells. J Exp Med 168, 157-170 (1988
27. Barton E. S., Lutzke M. L., Rochford R., & Virgin H. W. t. Alpha/beta interferons regulate murine gammaherpesvirus latent gene expression, and reactivation from latency. J Virol 79, 14149-14160 (2005
28. Decker T., Stockinger S., Karaghiosoff M., Muller M., & Kovarik P. IFNs, and STATs in innate immunity to microorganisms. J Clin Invest 109, 1271-1277 (2002
29. Pilz A., et al. Dendritic cells require STAT-1 phosphorylated at its transactivating domain for the induction of peptide-specific CTL. J Immunol 183, 2286-2293 (2009
30. Cella M., et al. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12, and enhances T cell stimulatory capacity: T-T help via APC activation. J Exp Med 184, 747-752 (1996
31. Kretschmer K., et al. Inducing, and expanding regulatory T cell populations by foreign antigen. Nat Immunol 6, 1219-1227 (2005
32. Peters A. L., Stunz L. L., & Bishop G. A. CD40, and autoimmunity: the dark side of a great activator. Semin Immunol 21, 293-300 (2009
33. Weck K. E., Barkon M. L., Yoo L. I., Speck S. H., & Virgin H. I. Mature B cells are required for acute splenic infection, but not for establishment of latency, by murine gammaherpesvirus 68. J Virol 70, 6775-6780 (1996
34. Sunil-Chandra N. P., Efstathiou S., Arno J., & Nash A. A. Virological, and pathological features of mice infected with murine gamma-herpesvirus 68. The Journal of general virology 73, 2347-2356 (1992
35. Sunil-Chandra N. P., Efstathiou S., & Nash A. A. Murine gammaherpesvirus 68 establishes a latent infection in mouse B lymphocytes in vivo. The Journal of general virology 73, 3275-3279 (1992
36. Jia Q., et al. Induction of protective immunity against murine gammaherpesvirus 68 infection in the absence of viral latency. J Virol 84, 2453-2465 (2010
37. Bennett S. R., et al. Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature 393, 478-480 (1998
38. Ferrer I. R., et al. Antigen-specific induced Foxp3+ regulatory T cells are generated following CD40/CD154 blockade. Proc Natl Acad Sci USA 108, 20701-20706 (2011
39. Grewal I. S., & Flavell R. A. CD40, and CD154 in cell-mediated immunity. Annu Rev Immunol 16, 111-135 (1998
40. Lanzavecchia A. Immunology. Licence to kill. Nature 393, 413-414 (1998
41. Martin S., Agarwal R., Murugaiyan G., & Saha B. CD40 expression levels modulate regulatory T cells in Leishmania donovani infection. J Immunol 185, 551-559 (2010
42. Ridge J. P., Di Rosa F., & Matzinger P. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper, and a T-killer cell. Nature 393, 474-478 (1998
43. Schoenberger S. P., Toes R. E., Van Der Voort E. I., Offringa R., & Melief C. J. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 393, 480-483 (1998
44. Stuber E., Strober W., & Neurath M. Blocking the CD40L-CD40 interaction in vivo specifically prevents the priming of T helper 1 cells through the inhibition of interleukin 12 secretion. J Exp Med 183, 693-698 (1996
45. Wiesemann E., et al. Effects of interferon-beta on co-signaling molecules: upregulation of CD40, CD86, and PD-L2 on monocytes in relation to clinical response to interferon-beta treatment in patients with multiple sclerosis. Mult Scler 14, 166-176 (2008
46. Marckmann S., et al. Interferon-beta up-regulates the expression of co-stimulatory molecules CD80, CD86, and CD40 on monocytes: significance for treatment of multiple sclerosis. Clin Exp Immunol 138, 499-506 (2004
47. Gasper-Smith N., Marriott I., & Bost K. L. Murine gamma-herpesvirus 68 limits naturally occurring CD4+ CD25+ T regulatory cell activity following infection. J Immunol 177, 4670-4678 (2006
48. Zozulya A. L., & Wiendl H. The role of regulatory T cells in multiple sclerosis. Nat Clin Pract Neurol 4, 384-398 (2008
49. Baecher-Allan C. M., et al. CD2 costimulation reveals defective activity by human CD4+ CD25(hi) regulatory cells in patients with multiple sclerosis. J Immunol 186, 3317-3326 (2011
50. Haas J., et al. Reduced suppressive effect of CD4+ CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Eur J Immunol 35, 3343-3352 (2005
51. Viglietta V., Baecher-Allan C., Weiner H. L., & Hafler D. A. Loss of functional suppression by CD4+ CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199, 971-979 (2004
52. Wingate P. J., McAulay K. A., Anthony I. C., & Crawford D. H. Regulatory T cell activity in primary, and persistent Epstein-Barr virus infection. J Med Virol 81, 870-877 (2009
53. Brooks J. W., et al. Requirement for CD40 ligand, CD4(+ ) T cells, and B cells in an infectious mononucleosis-like syndrome. J Virol 73, 9650-9654 (1999
54. Sarawar S. R., Lee B. J., Reiter S. K., & Schoenberger S. P. Stimulation via CD40 can substitute for CD4 T cell function in preventing reactivation of a latent herpesvirus. Proc Natl Acad Sci USA 98, 6325-6329 (2001
55. Huang W. X., Huang P., & Hillert J. Systemic upregulation of CD40, and CD40 ligand mRNA expression in multiple sclerosis. Mult Scler 6, 61-65 (2000
56. Gerritse K., et al. CD40-CD40 ligand interactions in experimental allergic encephalomyelitis, and multiple sclerosis. Proc Natl Acad Sci U S A 93, 2499-2504 (1996
57. Balashov K. E., Smith D. R., Khoury S. J., Hafler D. A., & Weiner H. L. Increased interleukin 12 production in progressive multiple sclerosis: induction by activated CD4+ T cells via CD40 ligand. Proc Natl Acad Sci USA 94, 599-603 (1997
58. Teleshova N., et al. Elevated CD40 ligand expressing blood T-cell levels in multiple sclerosis are reversed by interferon-beta treatment. Scand J Immunol 51, 312-320 (2000
59. Rastelli J., et al. LMP1 signaling can replace CD40 signaling in B cells in vivo, and has unique features of inducing class-switch recombination to IgG1. Blood 111, 1448-1455 (2008