The role of dendritic cells in T cell selection and survival

Abstract

Dendritic cells (DC) not only play an important role in the induction of immunity, but also have major functions in thymus and periphery in the absence of nominal antigen. In order to study these and other DC-functions in vivo, we expressed MHC class II I-E molecules under the control of the DC-specific CD11c promoter in C57B1/6 mice. With this targeted expression we were able to investigate DC functions in vivo without further manipulation of DC. We describe our findings with respect to the two major thymic events of negative and positive selection and demonstrate that DC are able and sufficient to induce negative selection of autoreactive CD4+ thymocytes by clonal deletion but do not induce positive selection. We further demonstrate in thymus-transplant experiments that DC play a major role in inducing survival of peripheral CD4+ mature T cells. This transgenic model therefore seems to be a valuable tool for the investigation of DC functions in vivo.