Viral immune evasion due to persistence of activated T cells without effector function

AJ Zajac, JN Blattman, K Murali-Krishna… - The Journal of …, 1998 - rupress.org
AJ Zajac, JN Blattman, K Murali-Krishna, DJD Sourdive, M Suresh, JD Altman, R Ahmed
The Journal of experimental medicine, 1998rupress.org
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 (CD69hi, CD44hi, CD62Llo) and proliferated in …
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 (CD69hi, CD44hi, 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.
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