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 IFN gamma-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.