The role of cytokines, CTLA-4 and costimulation in transplant tolerance and rejection.

T cell costimulation and cytokine production play an important role in generating the alloimmune responses that lead to allograft rejection. Recent data, however, provide evidence that costimulatory molecules, such as B7-1 and B7-2, and T cell activating cytokines, such as IFN-gamma and IL-2, also trigger negative feedback mechanisms in T lymphocytes which limit alloimmune responses. These feedback mechanisms are essential for the induction of long-term allograft acceptance and, in certain situations, transplantation tolerance.