Regulation of development and function of memory CD4 subsets

Immunologic memory refers to the dramatic response to previously encountere d antigen (Ag) that is largely controlled by CD4 T cells. Understanding how CD4 memory is regulated is essential for exploiting the immune system to p rotect against disease and to dampen immunopathology in allergic responses and autoimmunity. Using defined adoptive-transfer models, we are studying p arameters that affect differentiation of memory CD4 cells in vivo and have found that a complex interplay of T cell receptor signaling, costimulation, and cytokines can determine the extent of memory development and the balan ce of Th1 and Th2 memory subsets. On challenge, memory CD4 cells localize i n sites of Ag exposure and develop into effecters that regulate memory resp onses. We are investigating the roles of adhesion molecules, cytokines, and chemokines in the selective recruitment of CD4 memory subsets to address m echanisms by which memory T cells provide long-lasting immunity and, in our recent studies, to determine how memory CD4 cells contribute to the develo pment of autoimmune diabetes.