Role of CD4 T cell helper subsets in immune response and deviation of CD8 T cells in mice*

5 years ago

Role of CD4 T cell helper subsets in immune response and deviation of CD8 T cells in mice*

Yongjun Sui, Jay A. Berzofsky, William E. Paul, Alison Hogg, Shlomo Z. Ben-Sasson

The ability of different CD4+ T cell 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. CD4 subset Th1 cells help Tc1 cells that make IFN-γ, controlling virus infection. Th17 cells instead promote immune-deviation to Tc17 cells, making IL-17 and not controlling virus, thus providing inadequate help. IL-1β with TGF-β induce Th17 cells, so TGF-β blockade inhibits this immune deviation without blocking adjuvant effects of IL-1β.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/eji.201747091