Immunosuppression by Blocking α4-Integrins/VCAM-1 Adhesion
Allograft rejection is the expression of an immune reaction of the recipient against foreign antigens of the transplanted tissue and is mostly mediated by T lymphocytes. The initial step consists of T lymphocyte adhesion to graft endothelium, a process that is mediated by cell adhesion molecules. It has been shown that there are several pathways for recognition of alloantigens on the transplanted vascularized organs, and cell adhesion molecules play important roles in these processes. Adhesion is necessary for tightening of contact between T cells and antigen-presenting cells. Two signals are required for optimal clonal expansion of T cells: one from the T cell receptor upon binding to the major histocompatibility complex (MHC) antigen and the other signal from receptors that are distinctive from T cell receptors (Mueller et al. 1989; Schwartz et al. 1989; Schwartz 1990). Shaw et al. found that several adhesion molecules produce such costimulatory signals (Clevers et al. 1988; Shimizu et al. 1990a; Weaver and Unaue 1990). Schwartz et al. showed that, in the absence of the costimulatory signal, T cells become inactivated against the particular antigen, which leads to clonal anergy of the T cells (Mueller et al. 1989).
KeywordsMigration Integrin Cyclosporine Tacrolimus Nash
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