Cytokines in transplantation tolerance

Abstract

Transplantation tolerance is an immunologic state in which a transplant recipient's immune system does not mount a destructive immune response to an allograft. Tolerance offers an alternative to lifelong immunosuppression, potentially extending both allograft and patient survival by reducing transplant-related morbidity. Currently, the only clinically relevant approaches to achieve allograft tolerance rely on induction of donor hematopoietic chimerism through bone marrow or hematopoietic cell transplantation. There are two known types of T cell tolerance to alloantigens - central and peripheral. In central tolerance, alloantigen presentation in the thymic medulla results in clonal deletion of alloreactive immature lymphocytes. Peripheral tolerance is mediated by development of tolerogenic cell populations such as immature dendritic cells and regulatory T cells which suppress or delete alloreactive immune cells in the periphery. As the signaling molecules secreted by immune cells to orchestrate immune responses, cytokines are important in development of both central and peripheral tolerance and are critical in mediating both allograft rejection and tolerance. Understanding the immunology underlying the effects of cytokines on the immune system can help us to better understand their role in tolerance and to leverage that understanding to more reliably and safely induce transplantation tolerance.

Keywords: Allografts; Chimerism; Cytokines; Hematopoietic cell transplantation; Immunity; Immunosuppression therapy; T-lymphocytes; Transplantation tolerance.