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Xenogeneic thymus transplantation can efficiently induce specific immune tolerance to donor antigens in athymic recipients.However,many nude mice snffer from autoimmune diseases(AID) for over 10 weeks after xenogeneic thymus transplantation.CD4+CD25+Foxp3+ regulatory T (Treg)cells were recently determined to play a pivotal role in keeping immune tolerance in humans and mice.Thus,we investigated this subpopulation of Treg cells in the periphery of pig thymus-grafted nude mice suffering from AID.Our results showed that the expression of Foxp3, CTLA-4 and GITR on mouse CD4+CD25+T cells and the ratio of CD4+CD25+Foxp3+Treg cells to CD4+T cells were significantly decreased in the periphery of pig thymus-grafted nude mice snfiering from AID,compared with healthy pig or mouse thymus-grafted nude mice.Furthermore,mouse CD4+CD25+T cells in pig thymus-grafted nude mice Sufiering from AID showed more severe deficiency in immunosuppressive function compared with the counterpart in xenogeneic pig or syngeneic thymus-grafted nude mice without AID.Thus,the decreased frequency, altered phenotype and functional deficiency of mouse CD4+CD25+Treg cells in pig thymus-grafted nude mice may contribute to the development of AID in this model.