Human CD4+CD25+ regulatory T cells suppress anti-porcine xenogeneic responses.
Due to the shortage of human organs, xenotransplantation is being explored as an alternative to allotransplantation, but immune rejection remains a major hurdle to its implementation. We tested the ability of human CD4+CD25+ T cells (Treg cells) to suppress CD4+ T cell-mediated anti-porcine xenoresponses usingin vitroassays. Human Treg cells were hyporesponsive to porcine cell stimulation and suppressed the proliferative response of CD4+CD25- T cells in a dose-dependent manner, and comparison of the allo- and xenoresponses indicated that more Treg cells might be required to suppress the xenogeneic response than the allogeneic response. Stimulation of CD4+CD25- T cells with porcine cells resulted in secretion of IFN-gamma, TNF-alpha, IL-10, IL-6 and IL-2, and Treg cells suppressed the secretion of these cytokines, as well as the CD4+CD25- T-cell cytolytic response against porcine cells. These results suggest a potential role for Treg cells in promoting xenograft survival.
Laboratory of Immunology and Virology, Division of Cellular and Gene Therapies, Office of Cellular, Tissue, and Gene Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland, USA. porterc@cber.fda.gov
Cynthia M
CM
Porter
Eda T
ET
Bloom
D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D013552:Swine / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D015478:Antigens, Heterophile; D016207:Cytokines; D015375:Receptors, Interleukin-2