Xenorecognition and xenoimmunity

Human T lymphocytes can respond against pig stimulator cells according to a direct pathway of activation, indicating that no major differences exist between human T cell mediated alloresponses and xenospecific responses against pig stimulator cells in vitro. However, even if pig PBMC can activate T cells directly, it is believed that porcine islet cell clusters are incapable of activating cellular immunity directly in vivo, since ICC xenotransplants are thought to lack antigen-presenting cells. Therefore, specifically immunized T lymphocytes are not likely to be able to interact directly with xenogeneic target cells. We propose that xenogeneic transplants lacking antigen-presenting cells are subjected to antibody-dependent cell-mediated rejection mechanisms. The humoral xenoimmune response against pig antigens was swift and strong in all transplanted patients with peak antibody reactivities recorded on days 30-40. Titer increases in all lg-classes and subclasses were found. The humoral immune response was mainly, if not exclusively, directed against alpha-linked galactose-containing sugar residues, present on many different glycoproteins, including SLA class I antigens. There were no signs of de novo stimulation of B cell clones following xenoimmunization, rather an increased reactivity in cells producing xenospecific antibodies as part of the normal background of antibody production in healthy individuals. The findings form part of a basis for understanding xenoimmune mechanisms in man. The relatively homogeneous antibody specificities found both in normal and in immune patients are promising for future xenotransplantation using pig organs in man.