Format

Send to

Choose Destination
Immunol Cell Biol. 2016 Mar;94(3):293-305. doi: 10.1038/icb.2015.90. Epub 2015 Oct 15.

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 information

1
Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China.
2
Department of Medicine, School of Clinical Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge, UK.
3
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russian Federation.
4
University of Cambridge Metabolic Research Labs, Institute of Metabolic Science, Addenbrookes Hospital, Cambridge, UK.
5
Pirogov Russian National Research Medical University, Moscow, Russia.

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.

PMID:
26467610
DOI:
10.1038/icb.2015.90
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center