Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II

Lymphocyte activation gene-3 (LAG-3) is a CD4-related transmembrane protein expressed by regulatory T cells that binds MHC H on APCs. It is shown in this study that during Treg:DC interactions, LAG-3 engagement with MHC class II inhibits DC activation. MHC H cross-linking by agonistic Abs induces an ITAM-mediated inhibitory signaling pathway, involving Fc gamma R gamma and ERK-mediated recruitment of SHP-1 that suppresses dendritic cell maturation and inummostimulatory capacity. These data reveal a novel ITAM-mediated inhibitory signaling pathway in DCs triggered by MHC H engagement of LAG-3, providing a molecular mechanism in which regulatory T cells may suppress via modulating DC function.