Two functional subsets of FOXP3+ regulatory T cells in human thymus and periphery
Abstract
Previous studies suggest that thymus produces a homogenous population of natural regulatory T (Treg) cells that express a transcriptional factor FOXP3 and control autoimmunity through a cell-contact-dependent mechanism. We found two subsets of FOXP3+ natural Treg cells defined by the expression of the costimulatory molecule ICOS in the human thymus and periphery. Whereas the ICOS+FOXP3+ Treg cells used interleukin-10 to suppress dendritic cell function and transforming growth factor (TGF)-beta to suppress T cell function, the ICOS-FOXP3+ Treg cells used TGF-beta only. The survival and proliferation of the two subsets of Treg cells were differentially regulated by signaling through ICOS or CD28, respectively. We suggest that the selection of natural Treg cells in thymus is coupled with Treg cell differentiation into two subsets imprinted with different cytokine expression potentials and use both cell-contact-dependent and independent mechanisms for immunosuppression in periphery.
Key Biomarkers
Cited By (9)
- CD39+Foxp3+ regulatory T cells suppress pathogenic Th17 cells and are impaired in multiple sclerosisThe Journal of Immunology · 2009
- Pathogenic T cells have a paradoxical protective effect in murine autoimmune diabetes by boosting TregsJournal of Clinical Investigation · 2010
- Regulatory T cells and asthmaClinical & Experimental Allergy · 2009
- From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokinesNature Immunology · 2012
- Plasmodium falciparum–Mediated Induction of Human CD25hiFoxp3hi CD4 T Cells Is Independent of Direct TCR Stimulation and Requires IL-2, IL-10 and TGFβPLoS Pathogens · 2009
- Expression of the autoimmune susceptibility gene FcRL3 on human regulatory T cells is associated with dysfunction and high levels of programmed cell death-1The Journal of Immunology · 2010
- Interleukin-7 matures suppressive CD127(+) forkhead box P3 (FoxP3) (+) T cells into CD127(-) CD25(high) FoxP3 (+) regulatory T cells
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