Viral immune evasion due to persistence of activated T cells without effector function.
We examined the regulation of virus-specific CD8 T cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection of mice. Our study shows that within the same persistently infected host, different mechanisms can operate to silence antiviral T cell responses; CD8 T cells specific to one dominant viral epitope were deleted, whereas CD8 T cells responding to another dominant epitope persisted indefinitely. These virus-specific CD8 T cells expressed activation markers (CD69(hi), CD44(hi), CD62Llo) and proliferated in vivo but were unable to elaborate any antiviral effector functions. This unresponsive phenotype was more pronounced under conditions of CD4 T cell deficiency, highlighting the importance of CD8- CD4 T cell collaboration in controlling persistent infections. Importantly, in the presence of CD4 T cell help, adequate CD8 effector activity was maintained and the chronic viral infection eventually resolved. The persistence of activated virus-specific CD8 T cells without effector function reveals a novel mechanism for silencing antiviral immune responses and also offers new possibilities for enhancing CD8 T cell immunity in chronically infected hosts.
Zajac
A J
AJ
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Blattman
J N
JN
Murali-Krishna
K
K
Sourdive
D J
DJ
Suresh
M
M
Altman
J D
JD
Ahmed
R
R
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002908:Chronic Disease; D017635:Clonal Anergy / Q000276:immunology*; D017637:Clonal Deletion; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology; D008211:Lymphocyte Cooperation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology*; D015678:Viral Structural Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D015678:Viral Structural Proteins; D007371:Interferon-gamma