Role of CD4 Tcell helper subsets in immune response and deviation of CD8 Tcells in mice.

Abstract

The ability of different CD4+ Tcell subsets to help CD8+ T-cell response is not fully understood. Here, we found using the murine system that Th17 cells induced by IL-1β, unlike Th1, were not effective helpers for antiviral CD8 responses as measured by IFNγ-producing cells or protection against virus infection. However, they skewed CD8 responses to a Tc17 phenotype. Thus, the apparent lack of help was actually immune deviation. This skewing depended on both IL-21 and IL-23. To overcome this effect, we inhibited Th17 induction by blocking TGF-β. Anti-TGF-β allowed the IL-1β adjuvant to enhance CD8+ T-cell responses without skewing the phenotype to Tc17, thereby providing an approach to harness the benefit of common IL-1-inducing adjuvants like alum without immune deviation.