CD27-CD70 interactions sensitise naive CD4+ T cells for IL-12-induced Th1 cell development

Stimulation of CD27, a member of the tumour necrosis factor receptor family, by its ligand CD70 induces expansion of IFNgamma secreting CD4+ and CD8+ T cells in vivo. We here analysed the mechanisms through which CD27 mediates this effect. CD27 co-stimulation induced cell division but did not directly instruct naive CD4+ T cells to differentiate into IFNgamma-producing Th1 cells. Rather, in concert with signals delivered through the TCR-CD3 complex, CD27 co-stimulation enhanced the Th1-specific transcription factor T-bet and caused up-regulation of the IL-12Rbeta2 chain. Consequently, CD27-costimulated T cells yielded vast numbers of IFNgamma-secreting cells in response to IL-12. Additionally, CD27 ligation induced a strong up-regulation of Bcl-xL, but not of related anti-apoptotic molecules. Thus, CD27-CD70 interactions may promote Th1 formation by permitting naive T cells to respond to differentiation signals and by promoting survival of activated effector T cells.