Antibodies in the prevention of renal allograft rejection

The rejection of renal allografts is mediated largely by the intragraft accumulation of alloreactive T lymphocytes. Current immunosuppressive drugs impair lymphocyte function, but also have specific toxicities and lead to nonspecific impairment of immune responses, resulting in an increased risk of infections and malignancy. Initial studies examined the usefulness of antibodies that depleted lymphocytes in preventing rejection. More recently, antibodies that impair lymphocyte function by blocking the interleukin-2 receptor-alpha (IL-2Ralpha), thereby reducing IL-2-mediated activation of T cells, were shown to reduce the risk of rejection. As an additional strategy, antibodies that impair lymphocyte trafficking have been investigated for their effect on acute rejection. This review describes the results of clinical trials of depleting antilymphocyte antibodies, IL-2Ralpha blockers and antibodies to intercellular adhesion molecule-1, lymphocyte function-associated antigen-1, CD154 and CD52 in the prevention of allograft rejection. Particular emphasis has been placed on therapies for which there is evidence obtained from good, randomised, controlled trials or registry data.