The role of adhesion and costimulation molecules in graft-versus-host disease.

A cascade of signaling events directs and regulates the trafficking, homing and activation of T lymphocytes after allogeneic transplantation. These adhesion receptors include selectins, integrins and adhesion molecules of the immunoglobulin superfamily. Tissue-specific homing receptors direct the tissue-specific trafficking of T lymphocytes. When T cells encounter their antigen(s) presented by MHC molecules on APC, the antigen-specific signal mediated through the T-cell receptor (TCR) needs to be accompanied by additional costimulatory signals for complete T-cell activation to occur. The costimulatory signal determines the outcome of the first signal generated through the TCR, leading to either complete activation, partial activation or to a long-lasting state of antigen-specific unresponsiveness, termed anergy. Complete activation of T cells results in IL-2R (CD25) receptor expression, IL-2 production and T-cell proliferation.