Deficiency of Mouse CD4^+CD25^+Foxp3^+ Regulatory T Cells in Xenogeneic Pig Thymus-Grafted Nude Mice Suffering from Autoimmune Diseases  

作　　者：Baojun Zhang Chenming Sun Yanyan Qu Aijun Zhang Jun Liu Lianjun Zhang Zeqing Niu Yong Zhao 

机构地区：[1]Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China [2]China-U.S. Research Center for Life Sciences, Chinese Academy of Sciences, Beijing, China [3]State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Beijing 100101, China

出　　处：《Cellular & Molecular Immunology》2008年第5期325-332,共8页中国免疫学杂志（英文版）

基　　金：grants from the National Natural Science Foundation for Distinguished Young Scholars (C03020504, Y.Z.);Knowledge Innovation Program of Chinese Academy of Sciences (KSCX2-SW-333, Y.Z.);the Scientific Research Foundation for the Returned Overseas Chinese Scholars of State Education Ministry (2005-546, Y.Z.)

摘　　要：Xenogeneic thymus transplantation can efficiently induce specific immune tolerance to donor antigens in athymic recipients. However, many nude mice suffer 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 suffering from AID, compared with healthy pig or mouse thymus-grafted nude mice. Furthermore, mouse CD4^＋CD25^＋ T cells in pig thymus-grafted nude mice suffering 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.Xenogeneic thymus transplantation can efficiently induce specific immune tolerance to donor antigens in athymic recipients. However, many nude mice suffer 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 suffering from AID, compared with healthy pig or mouse thymus-grafted nude mice. Furthermore, mouse CD4^＋CD25^＋ T cells in pig thymus-grafted nude mice suffering 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.

关 键 词：regulatory T cell FOXP3 autoimmune disease PIG thymus transplantation 

分 类 号：R593[医药卫生—内科学]