Novel Memory CD4T Cell Subset Negatively Regulates Maturation And Function Of Dendritic Cells And The Underlying Mechanisms

Immunological memory is one of the features of immune system. Rare memory cells can greatly affect secondary immune response, but how they exert this effect is not fully understood. Dendritic cells (DCs) are professional antigen-presenting cells, and functional states and different subsets of DCs determine the differentiation routes of specific immune cells and immune response magnitude, playing key roles in both initiating immune response and inducing immune tolerance. Now, it is found that DCs play important roles in the generation of various T cell subsets including memory T cells. It is difficult to obtain enough memory CD4T cells for functional studies due to their rare frequency in vivo. So there are few studies about the interaction between memory CD4T cells and other immune cell subsets, and it is still not clear how memory CD4T cells regulate DC functions and the underlying mechanisms.In previous study, we found that regulatory DCs could program generation of IL-4/IL-10-producing alternative memory CD4T cells (Tm2cells), which inhibited CD4T cell proliferation initiated by mature DCs via IL-10. Meanwhile, we also established one unique in vitro culture system of preparing enough number of these memory CD4T cell subsets for their functional studies. In this study, we further investigated direct regulation of DCs by Tm2cells and underlying mechanisms. We found that Tm2could inhibit expression of costimulatory molecules CD80and CD86on DCs, and Tm2-educated DCs secreted lower IL-6, IL-1β and IL-12p70with lower ability to induce proliferation and activation of naive CD4T cells. Suppression of DC functions by Tm2is dependent on antigen-specific activation of Tm2, and IL-4, IL-10secretion of Tm2. And in vivo, Tm2could inhibit CD86expression on DCs in the draining lymph nodes when mice were immunized by antigen peptide. Our results indicate that memory CD4T cells can regulate functional states of DCs, exerting and amplifying the Tm's effects and then modulating secondary immune response. This study will help to understand the effects and mechanisms of memory T cells and fine regulation of DC functions by memory CD4T cells during secondary immune response further, providing theoretic basis for vaccine design and application.