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

T cell costimulation and cytokine production play an important role in gene rating the alloimmune responses that lead to allograft rejection. Recent da ta, however, provide evidence that costimulatary molecules, such as B7-1 an d B7-2, and T cell activating cytokines, such as IFN-gamma and IL-2, also t rigger negative feedback mechanisms in T lymphocytes which limit alloimmune responses. These feedback mechanisms are essential for the induction at lo ng-term allograft acceptance and, in certain situations, transplantation to lerance.