Luca Inverardi

Early Events in Cell-Mediated Recognition of Vascularized Xenografts: Cooperative Interactions between Selected Lymphocyte Subsets and Natural Antibodies

Cell-mediated early immune recognition of xenogeneic vascularized discordant grafts is poorly characterized. It has been the purpose of our studies to elucidate the role of lymphocytes in the recognition and rejection phenomena. To this end, we have utilized both ex vivo and in vitro model systems. We demonstrate that selected human lymphocyte subpopulations (mainly NK cells) rapidly and specifically adhere to xenogeneic endothelia. Efficient lysis of endothelial cells is subsequently mediated by such a population. Adhesion and cytotoxicity occur via at least two pathways, one dependent on and the other independent of the presence of human natural antibodies of the G class. Both IgG-dependent and IgG-independent adhesion and cytotoxicity can be partly inhibited by the use of anti-leukocyte integrin monoclonal antibodies. IgG-dependent adhesion and cytotoxicity can be also partly inhibited by carbohydrate structures that contain the alpha-galactosyl epitope. A possible role of these events in the eventual outcome of discordant vascularized xenogeneic transplants can be postulated.