The alloimmune response and effector mechanisms of allograft rejection.

Allograft rejection is the consequence of the recipient's alloimmune response to nonself antigens expressed by donor tissues. Allospecific T lymphocytes are activated by donor peptides which are presented in the context of major histocompatibility complex molecules by either donor or recipient antigen presenting cells. Antigen presenting cells also provide essential costimulatory signals which are required for T cell proliferation and differentiation into either helper or effector lymphocytes. Effector mechanisms of allograft rejection include those mediated by cytotoxic T lymphocytes, macrophages, natural killer cells, and B lymphocytes. Importantly, alloimmune responses are controlled by regulatory molecules which include membrane receptors and cytokines. Novel insights into the interactions between antigen presenting cells and T lymphocytes, and further understanding of how alloimmune responses are regulated, will help in developing effective antirejection and tolerance-inducing strategies.