T cell and B cell responses in transplantation

The birth of the transplantation field motivated studies of the adaptive immune system; in particular, the self-nonself discrimination by T and B cells. Nevertheless, 59 years have passed since Medawar and his colleagues described the concept of acquired immune tolerance to alloantigens in mice, and the survival of human transplants still depends on continual use of immunosuppressive drugs that non-selectively impair immune cell function. This chapter reviews the basic biology of T cells, the central role of T cell responses in rejecting transplanted organs, as well as the T cell-directed therapeutic approaches that aim to induce transplantation tolerance. The contributions of B cells and alloantibody in acute allograft injury, chronic rejection, and transplantation tolerance will also be discussed. Despite the more in depth characterization of the molecular mechanisms underlying T cell and B cell responses in transplantation, current approaches targeting molecules expressed by immune cells have failed to create immune tolerance to allografts. The concepts described in this chapter reveal that a successful tolerogenic therapy for transplantation would not only block the activation signals for alloreactive T and B cells, but also should create an extrinsic tolerogenic environment and turn on the intrinsic negative regulators to terminate their responses.