The T Cell Response to Transplantation Antigens

Tlymphocytes are critical mediators of transplant rejection. T cells recognize donor antigens that are directly expressed on donor cells and also recognize donor-derived antigens that recipient cells process and present upon recipient MHC molecules. When stimulated with their cognate antigens in the context of appropriate costimulatory signals, alloreactive T cells undergo activation and differentiation into helper and effector cells of various phenotypes. Cytokine-secreting CD4 T cells provide helper signals for B cell activation to produce alloantibody and for optimal activation/expansion of effector CD8 T cells. Activated T cells and alloantibodies injure the allograft through a host of effector mechanisms. Under tolerogenic conditions, regulatory T cells expand and differentiate, limiting the differentiation and function of the effector cells. Understanding mechanisms of alloreactive T cell function has helped to explain mechanisms of currently used immunosuppressants and can guide the development of novel therapies.