Memory CD4 T cells induce selective expression of IL-27 in CD8+ dendritic cells and maintain homeostatic control of naïve T cell proliferation (104.8)

Abstract

Abstract Naïve CD4 T cells undergo robust proliferation in lymphopenic conditions, while they remain quiescent in steady-state conditions. Mechanisms involved in the induction of the proliferation have been extensively examined. However, a mechanism of how naïve T cells are kept from proliferating under steady-state conditions remains unclear. Here we demonstrate that memory CD4 T cells directly inhibit naïve T cell proliferation within lymphopenic hosts by modulating stimulatory functions of DCs. The inhibition occurred only when both memory and naïve CD4 T cells interact with the same DCs. Thus, when naïve CD4 T cells were introduced into a recipient where a portion of DCs do not interact with memory CD4 T cells, the inhibition was lost. Moreover, the inhibition was mediated by DC-derived IL-27, which was directly induced in CD8+ DC subsets following CD4 T cell-DC interaction. IL-27 appeared to be the major mediator of inhibition as naïve T cells deficient in IL-27R were resistant to memory CD4 T cell mediated inhibition. Finally, IL-27-mediated regulation of memory T cell homeostasis was also observed in steady-state conditions. Taken together, we propose a new model for maintaining peripheral T cell homeostasis via memory CD4 T cells and CD8+ DC-derived IL-27 in vivo.