Late-Rising Cd4 T Cells Resolve Viral Persistence

Abstract Robust CD4 T cell responses help to control chronic infection and restrict disease, but their specific requirements for resolving viral persistence remain poorly defined. During mouse cytomegalovirus (MCMV) infection, CD4 T cells recognizing an epitope derived from the viral M09 protein expand at late times of infection and display a unique phenotype compared to their conventional counterparts, including high IFNγ-production and low expression of the activated CD43 isoform. Ablating these late-rising CD4 T cells by mutating the MCMV M09 genomic epitope, or inducing them through vaccination, revealed their critical role in resolving persistent replication by overcoming IL-10 mediated immune suppression. Together, these data show that unique subsets of late-rising CD4 T cells are qualitatively superior in resolving chronic infection when compared to those that expand earlier, results that should be considered for vaccine development.