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.
Satake
M
M
Department of Clinical Immunology, Karolinska Institute, Huddinge Hospital, Sweden.
Kumagai-Braesch
M
M
Kawagishi
N
N
Möller
E
E
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D003920:Diabetes Mellitus / Q000276:immunology / Q000601:surgery; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D016030:Kidney Transplantation / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology; D016377:Organ Transplantation / Q000379:methods*; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology; D014183:Transplantation, Heterologous