TY - JOUR
T1 - Viral immune evasion due to persistence of activated T cells without effector function
AU - Zajac, Allan J.
AU - Blattman, Joseph N.
AU - Murali-Krishna, Kaja
AU - Sourdive, David J.D.
AU - Suresh, M.
AU - Altman, John D.
AU - Ahmed, Rafi
PY - 1998
Y1 - 1998
N2 - 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), CD62L(lo)) 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.
AB - 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), CD62L(lo)) 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.
KW - CD4 T cells
KW - Chronic infections
KW - Cytotoxic T cells
KW - Major histocompatibility complex tetramers
KW - Unresponsiveness
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U2 - 10.1084/jem.188.12.2205
DO - 10.1084/jem.188.12.2205
M3 - Article
C2 - 9858507
AN - SCOPUS:0032416085
SN - 0022-1007
VL - 188
SP - 2205
EP - 2213
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 12
ER -