Achievement of cellular immunity and discordant xenogeneic tolerance in mice by porcine thymus grafts.
Specific cellular immune tolerance may be essential for successful xenotransplantation in humans. Thymectomized (ATX), T and NK cell-depleted immunocompetent mice grafted with xenogeneic fetal pig thymic and liver tissue (FP THY/LIV) result in efficient mouse thymopoiesis and peripheral repopulation of functional mouse CD4(+) T cell. Very importantly, the reconstituted mouse T cells are specifically tolerant to pig donor antigens. Studies demonstrated that porcine MHCs mediated positive and negative selection of mouse thymocytes in FP THY grafts, whereas mouse MHCs were involved in negative selection in grafts. Therefore, T cell tolerance to xenogeneic donor antigens could be induced by grafting donor thymus tissue. Xenogeneic thymic replacement might have a potential role in the reconstitution of cellular immunity in patients with AIDS or other immunodeficiencies caused by thymus dysfunction.
Zhao
Yong
Y
Transplantation Biology Research Division, State Key Lab of Membrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China. zhaoy@panda.ioz.ac.cn
Sun
Zuyue
Z
Sun
Yimin
Y
Langnas
Alan N
AN
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000628:therapy; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008099:Liver / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology; D051379:Mice; D013552:Swine; D013556:Swine, Miniature; D013950:Thymus Gland / Q000276:immunology* / Q000637:transplantation; D023001:Transplantation Tolerance / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000276:immunology*