Regulation of development and function of memory CD4 subsets.

Immunologic memory refers to the dramatic response to previously encountered antigen (Ag) that is largely controlled by CD4 T cells. Understanding how CD4 memory is regulated is essential for exploiting the immune system to protect against disease and to dampen immunopathology in allergic responses and autoimmunity. Using defined adoptive-transfer models, we are studying parameters 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 balance of Th1 and Th2 memory subsets. On challenge, memory CD4 cells localize in sites of Ag exposure and develop into effectors that regulate memory responses. We are investigating the roles of adhesion molecules, cytokines, and chemokines in the selective recruitment of CD4 memory subsets to address mechanisms by which memory T cells provide long-lasting immunity and, in our recent studies, to determine how memory CD4 cells contribute to the development of autoimmune diabetes.