LCMV-specific CD4 T cells induce immunopathology and impair immune protection following chronic LCMV infection (VIR1P.1132)

CD4 T cells promote memory immune responses, but it is unclear whether vaccine-induced CD4 T cells contribute to immune protection. We interrogated if virus-specific CD4 T cells would protect mice against infection with chronic lymphocytic choriomeningitis virus (LCMV). Immunization with vaccines that induced CD4 T cell responses resulted in mortality following infection with persistent strains of LCMV. Immunopathology was associated with high levels of virus-specific CD4 T cells, generalized inflammation and collapse of adaptive immunity. Interestingly, virus-specific CD8 T cells or antibodies abrogated these lethal effects of CD4 T cell vaccines. Our data demonstrate the importance of tightly regulating CD4 T cell responses following vaccination, and suggest that CD4 T cells in the absence of effective antiviral immune responses could induce lethal immunopathology.