Physiologic basis of transplantation

Successful clinical transplantation is limited not by technical pitfalls but rather by the immune process that mediates rejection of the transplanted tissue or organ (1). Thus, the physiologic basis of transplantation rests on understanding the immunologic rejection process. The goal of the transplant surgeon is to manipulate either the host (i.e., the recipient of the transplanted organ or tissue) or the allograft (i.e., the organ or tissue being transplanted from a donor, within the same species) to avert, minimize, or reduce this physiologic process. Immunologic events leading to allograft rejection can be divided into afferent, central, and efferent limbs. The afferent limb is the initiation of immune responses, which includes presentation of foreign histocompatibility antigens to T-lymphocytes by antigen-presenting cell (APC). The activation of antigen-nonspecific innate immunity is critical for this process, which by itself is also able to directly cause damage to allografts. The central limb is the activation of alloantigen-specific T- and B-lymphocytes, including their proliferation and differentiation. The efferent limb is execution of effector functions of activated lymphocytes, including both cellular and soluble cytotoxicities to destroy grafts. In the following discussion, we will use alloreactive T-cells as an example, and provide a mechanistic overview of various components of alloimmune responses and how alloimmune responses proceed.