title: TCR usage, gene expression and function of two distinct FOXP3(+)Treg subsets within CD4(+)CD25(hi) T cells identified by expression of CD39 and CD45RO.
abstract: FOXP3+ regulatory T (Treg) cells are indispensable for immune homeostasis, but their study in humans is complicated by heterogeneity within Treg, the difficulty in purifying Tregs using surface marker expression (e.g. CD25) and the transient expression of FOXP3 by activated effector cells. Here, we report that expression of CD39 and CD45RO distinguishes three sub-populations within human CD4(+)CD25(hi) T cells. Initial phenotypic and functional analysis demonstrated that CD4(+)CD25(hi)CD39(+)CD45RO(+) cells had properties consistent with effector Treg, CD4(+)CD25(hi)CD39(-)CD45RO(-) cells were naïve Treg and CD4(+)CD25(hi)CD39(-)CD45RO(+) cells were predominantly non-Treg with effector T-cell function. Differences in these two newly identified Treg subsets were corroborated by studies of gene expression and TCR analysis. To apply this approach, we studied these two newly identified Treg subsets in ankylosing spondylitis, and showed impairment in both effector and naïve Treg. This work highlights the importance of discriminating Treg subsets to enable proper comparisons of immune regulatory capacity in healthy individuals and those with inflammatory disease.
authors.affiliation: Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Lingying
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Medicine, School of Clinical Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge, UK.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Goodall
authors.affiliation: Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Putintseva
authors.affiliation: University of Cambridge Metabolic Research Labs, Institute of Metabolic Science, Addenbrookes Hospital, Cambridge, UK.
authors.forename: Brian
authors.initials: B
authors.lastname: Lam
authors.affiliation: Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.affiliation: University of Cambridge Metabolic Research Labs, Institute of Metabolic Science, Addenbrookes Hospital, Cambridge, UK.
authors.forename: Giles
authors.initials: G
authors.lastname: Yeo
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russian Federation.|Pirogov Russian National Research Medical University, Moscow, Russia.
authors.forename: Mikhail
authors.identifier: http://orcid.org/0000-0001-7826-7942
authors.initials: M
authors.lastname: Shugay
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russian Federation.|Pirogov Russian National Research Medical University, Moscow, Russia.
authors.forename: Dmitriy M
authors.identifier: http://orcid.org/0000-0003-0430-790X
authors.initials: DM
authors.lastname: Chudakov
authors.affiliation: Department of Medicine, School of Clinical Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge, UK.
authors.forename: Hill
authors.initials: H
authors.lastname: Gaston
authors.affiliation: Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Huji
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D056747:Immunomodulation; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013167:Spondylitis, Ankylosing / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D015415:Biomarkers; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta