Human renal allograft rejection: Immune mechanisms, molecular correlates and treatment strategies

Renal allograft rejection is dependent upon the co-ordinated activation of alloreactive T cells and antigen-presenting cells (APC) such as monocyte-macrophages, dendritic cells and B cells. Whereas acute rejection is a T cell-dependent process, a broad array of effector mechanisms participate in the destruction of the allograft. Through the release of cytokines and cell-to-cell interactions, a diverse assembly of lymphocytes, including CD4+ cells, CD8+ cytotoxic T cells, antibody-forming B cells, and other pro-inflammatory leucocytes are recruited into the anti-allograft response. In this review, we discuss immune effector mechanisms, molecular correlates of rejection and therapeutic protocols. The recent expansion in our knowledge, coupled with the discovery and use of new immunosuppressants in the clinic, engenders optimism regarding management of allograft rejection, the most serious frequent complication in organ transplantation.