title: Retention and tolerance of autoreactive CD4(+) recent thymic emigrants in the liver.
abstract: Mechanisms of peripheral tolerance play a critical role in preventing T cells that escape from negative selection in the thymus from initiating autoimmune reactions. To investigate the site of peripheral tolerance induction, we examined migration and activation of recent thymic emigrants (RTEs) in liver, spleen, lymph node and peripheral blood. We show that a fraction of RTE precursors were retained in the liver independent of the secondary lymphoid organs. Compared to RTEs from the lymph nodes, RTEs from the liver proliferated more and many exhibited an activated phenotype with the capability of producing IL-10 upon activation. Liver RTEs also responded poorly to interleukin (IL)-7 and were more prone to apoptosis. Following transfer into RAG(-/-) recipients, liver RTEs induced more severe inflammation and T cell infiltration in the lung and colon. The extrathymic expression of MHC and Aire is required for the acquisition of tolerogenic phenotype of newly generated thymic emigrants in the liver. These results suggest that the liver is the first checkpoint in the periphery to filter, retain, and enforce tolerance to autoreactive CD4(+) thymic emigrants that escape from negative selection.
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Xu
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China.
authors.forename: Shusong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jin
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Li
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Lin
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hao
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China.
authors.forename: Xiuyuan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Pang
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Qian
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Peking University Medical and Health Analytical Center, Peking University Health Science Center, Beijing, PR China. Electronic address: wuhounan@bjmu.edu.cn.
authors.forename: Hounan
authors.initials: H
authors.lastname: Wu
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China. Electronic address: zhangyu007@bjmu.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100191, PR China. Electronic address: qingge@bjmu.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ge
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D015551:Autoimmunity / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D016753:Interleukin-10 / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D008099:Liver / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000096927:AIRE Protein
chemical_list: D000954:Antigens, Surface; D006649:Histocompatibility Antigens; D016753:Interleukin-10; D015851:Interleukin-7; D014157:Transcription Factors; D000096927:AIRE Protein
keywords: Liver; Lymphocyte infiltration; Mature naïve T cells; Recent thymic emigrants; Tolerance