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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
Author(s) -
Ye Lingying,
Goodall Jane C,
Zhang Libin,
Putintseva Ekaterina V,
Lam Brian,
Jiang Lei,
Liu Wei,
Yin Jian,
Lin Li,
Li Ting,
Wu Xin,
Yeo Giles,
Shugay Mikhail,
Chudakov Dmitriy M,
Gaston Hill,
Xu Huji
Publication year - 2016
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2015.90
Subject(s) - il 2 receptor , foxp3 , effector , biology , immune system , immunology , phenotype , t cell , microbiology and biotechnology , gene , genetics
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.