The immune response to kidney allograft. Part II: The role of costimulatory and accessory molecules in T-cell activation; The effector phase of response

摘要

Kidney transplantation causes an immune response to non-self antigens called allograft rejection. The response to a kidney allograft can be divided into three phases: recognition of the alloantigen, activation of antigen-specific lymphocytes, and the effector phase of graft rejection. Full T-cell activation requires two distinct signals: one through the TCR and a second costimulatory signal through accessory molecules. These accessory molecules play two important roles. The first is to maintain contact between the T cells and APCs, thus providing time for the TCR to sample the antigen on the APC (ICAM-1/LFA-1). The second role is to cooperate with TCR-initiated signals in T-cell activation. The most important second costimulatory signals influencing T-cell clonal expansion and differentiation are provided by the B7/CD28 family of molecules. In the effector phase of graft rejection, foreign cells are damaged by means of three possible mechanisms: 1) T-cell cytotoxicity, 2) delayed-type hypersensitivity, and 3) antibody-dependent cell-mediated cytotoxicity