4-1BB costimulation enhances HSV-1-specific CD8 + T cell responses by the induction of CD11c +CD8 + T cells

Abstract

Since 4-1BB plays a predominant role in CD8 + T cell responses, we investigated the effects of 4-1BB triggering on the primary and memory CD8 + T responses to HSV-1 infection. 4-1BB was detected on 10–15% of CD4 + and CD8 + T cells following the infection. 4-1BB-positive T cells were in the proliferative mode and showed the enhanced expression of anti-apoptotic proteins. Agonistic anti-4-1BB treatment exerted preferential expansion of CD8 + T cells and gB/H-2K b-positive CD8 + T cells, and enhanced cytotoxicity against HSV-1 that was mainly mediated by CD11c +CD8 + T cells. CD11c +CD8 + T cells were re-expanded following re-challenge with HSV-1 at post-infection day 50, indicating that CD11c +CD8 + phenotype was maintained in memory CD8 + T cell pool. Our studies demonstrated that 4-1BB stimulation enhanced both primary and memory anti-HSV-1 CD8 + T cell responses, which was mediated by a massive expansion of antigen-specific CD11c +CD8 + T cells.