Effector mechanisms of rejection

Abstract

Organ transplantation appears today to be the best alternative to replace the loss of vital organs induced by various diseases. Transplants can, however, also be rejected by the recipient. In this review, we provide an overview of the mechanisms and the cells/molecules involved in acute and chronic rejections. T cells and B cells mainly control the antigen-specific rejection and act either as effector, regulatory, or memory cells. On the other hand, nonspecific cells such as endothelial cells, NK cells, macrophages, or polymorphonuclear cells are also crucial actors of transplant rejection. Last, beyond cells, the high contribution of antibodies, chemokines, and complement molecules in graft rejection is discussed in this article. The understanding of the different components involved in graft rejection is essential as some of them are used in the clinic as biomarkers to detect and quantify the level of rejection.

Figure 1.

Chemokines: Homing of immune cells and role in acute rejection. Mononuclear cells are able to migrate into the graft or into the lymphoid organs in response to chemokine gradients. Experiments on animal models of transplantation and analysis of human samples from transplant recipients allow a better understanding of the involvement of chemokines in graft rejection.

Figure 2.

Induction of endothelial cells activation by antidonor antibodies. Antidonor antibodies (Abs) are known to induce chronic allograft rejection by several mechanisms of action involving their constant domain (Fc) or their capacity to induce activation of complement. Antidonor Abs also induce endothelial cell activation. Activated ECs secrete notably growth factors (GF) that induce the recruitment and activation/proliferation of several cells implicated in allograft rejection.