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Eur J Immunol. 2014 Sep;44(9):2703-11. doi: 10.1002/eji.201344392. Epub 2014 Jun 16.

Enhanced suppressor function of TIM-3+ FoxP3+ regulatory T cells.

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  • 1Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT, USA.

Abstract

T-cell immunoglobulin and mucin domain 3 (TIM-3) is an Ig-superfamily member expressed on IFN-γ-secreting Th1 and Tc1 cells and was identified as a negative regulator of immune tolerance. TIM-3 is expressed by a subset of activated CD4(+) T cells, and anti-CD3/anti-CD28 stimulation increases both the level of expression and the number of TIM-3(+) T cells. In mice, TIM-3 is constitutively expressed on natural regulatory T (Treg) cells and has been identified as a regulatory molecule of alloimmunity through its ability to modulate CD4(+) T-cell differentiation. Here, we examined TIM-3 expression on human Treg cells to determine its role in T-cell suppression. In contrast to mice, TIM-3 is not expressed on Treg cells ex vivo but is upregulated after activation. While TIM-3(+) Treg cells with increased gene expression of LAG3, CTLA4, and FOXP3 are highly efficient suppressors of effector T (Teff) cells, TIM-3(-) Treg cells poorly suppressed Th17 cells as compared with their suppression of Th1 cells; this decreased suppression ability was associated with decreased STAT-3 expression and phosphorylation and reduced gene expression of IL10, EBI3, GZMB, PRF1, IL1Rα, and CCR6. Thus, our results suggest that TIM-3 expression on Treg cells identifies a population highly effective in inhibiting pathogenic Th1- and Th17-cell responses.

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEYWORDS:

FoxP3; Regulatory T (Treg) cells; TIM-3; Th17

PMID:
24838857
[PubMed - indexed for MEDLINE]
PMCID:
PMC4165702
[Available on 2015-09-01]

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