Comparison of activation versus induction of unresponsiveness of virus-specific CD4+ and CD8+ T cells upon acute versus persistent viral infection.

The functional status of CD4+ T cells during establishment of persistent infection with the noncytopathic lymphocytic choriomeningitis virus was assessed and compared to that of cytotoxic CD8+ T cells. Functionality of virus-specific CD4+ T cells was measured by proliferative responses, cytokine secretion, cognate help, and IFNgamma-mediated protection against challenge infection with recombinant vaccinia virus. Functional CD4+ T cells were induced early after infection and remained measurable up to 6 weeks but then were rendered unresponsive. In contrast, CD8+ T cells were functionally inactivated within 10-15 days. Importantly, functional inactivation of virus-specific CD4+ T cells during persistent viral infection seemed to be critical for the survival of the host.