Th17 cells differentiated without TGF-β undergo FasL-dependent AICD (P1183)

Abstract

Abstract Interleukin (IL)-17-producing T helper (Th17) cells can be differentiated under the combination of cytokines: IL-6, a proinflammatory cytokine, and transforming growth factor (TGF) beta, an antiinflammatory cytokine. We previously reported that TGF-beta is acting indirectly for Th17 cell differentiation by blocking expression of the transcription factors signal transducer and activator of transcription (STAT) 4 and GATA-3, thus preventing Th1 and Th2 cell differentiation. From T cells derived from Stat-6(-/-)T-bet(-/-) mice, which are unable to generate Th1 and Th2 cells, IL-6 alone can induce robust differentiation of Th17 cells. Here we report that Th17 cells derived from Stat-6(-/-)T-bet(-/-) mice, which were differentiated without TGF-β, underwent FasL-dependent activation-induced cell death (AICD). FasL was up-regulated upon TCR reactivation of those Th17 cells and the addition of FasL blocking antibodies abolished those Fas induced Th17 cell death. These features were comparable to wild type Th17 cells differentiated under the traditional combination condition of IL-6 and TGF-β. In all, these data demonstrate that Th17 cells differentiated without TGF-β undergo FasL-dependent AICD in a similar way to those wild type Th17 cells differentiated with TGF-β, indicating that Th17 cells derived from these two different conditions share common characteristics in AICD.