Multifront assault on antigen presentation by Japanese encephalitis virus subverts CD8+ T cell responses.
Japanese encephalitis virus (JEV) is a frequent cause of acute and epidemic viral encephalitis. However, there is little information describing the mechanisms by which JEV subverts immune responses that may predispose the host to secondary infections. In this study, we found that JEV induced the subversion of CD8(+) T cell responses in a transient manner that was closely correlated with viral multiplication. Subsequently, analysis using a TCR-transgenic system revealed that CD8(+) T cells purified from JEV-infected mice showed impaired responses, and that naive CD8(+) T cells adoptively transferred into JEV-infected recipients showed less expanded responses. Furthermore, JEV altered the splenic dendritic cell (DC) subpopulation via preferential depletion of CD8alpha(+)CD11c(+) DCs without changing the plasmacytoid DCs and induced a significant reduction in the surface expression of MHC class II and CD40, but not MHC class I, CD80, and CD86 molecules. Finally, JEV was shown to inhibit the presentation of MHC class I-restricted Ag in DCs, and this immune suppression was ameliorated via the activation of DCs by TLR agonists. Collectively, our data indicate that JEV precludes the functions of Ag-presenting machinery, such as depletion of CD8alpha(+)CD11c(+) DCs and downregulation of MHC class I-restricted Ag presentation, thereby leading to immune subversion of CD8(+) T cells.
Aleyas
Abi G
AG
College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Jeonju City 561-756, Republic of Korea.
Han
Young Woo
YW
George
Junu A
JA
Kim
Bumseok
B
Kim
Koanhoi
K
Lee
Chong-Kil
CK
Eo
Seong Kug
SK
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D039521:CD11c Antigen / Q000096:biosynthesis / Q000378:metabolism; D016827:CD8 Antigens / Q000096:biosynthesis / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002522:Chlorocebus aethiops; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D004664:Encephalitis Virus, Japanese / Q000276:immunology* / Q000472:pathogenicity*; D004672:Encephalitis, Japanese / Q000276:immunology / Q000473:pathology / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology; D057131:Immune Evasion / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014709:Vero Cells
D039521:CD11c Antigen; D016827:CD8 Antigens; C431698:CD8alpha antigen; D018984:Epitopes, T-Lymphocyte