CD4(+) CD25(low) GITR(+) cells: a novel human CD4(+) T-cell population with regulatory activity.

Treg subsets play a role in sustaining peripheral tolerance, are characterized by markers such as forkhead winged-helix transcription factor (FOXP3) and CD25, and produce suppressive cytokines, such as IL-10 and TGF-β. Glucocorticoid-induced TNF receptor family-related (GITR) protein has been suggested to regulate Treg activity in mice. The aim of our study was to investigate GITR expression in human CD4(+) T lymphocytes and its possible role in Treg function. Results indicate that a subset of CD4(+) T cells in the peripheral blood expresses GITR and low levels of CD25 (CD4(+) CD25(low) GITR(+) ). These cells show Treg features as they express FOXP3, IL-10, TGF-β and are anergic but, as opposed to natural Tregs, express low levels of CTLA-4 and are CD127(high) . CD4(+) CD25(low) GITR(+) cells represent a low percentage of the CD4(+) T-cell population (0.32-1.74%) and are mostly memory cells. Functional experiments demonstrated that CD4(+) CD25(low) GITR(+) cells have relevant suppressive activity that depends on TGF-β. Moreover, an anti-GITR Ab inhibited their suppressive activity, as observed in CD4(+) CD25(+) murine Tregs. Taken together, these data indicate that human CD4(+) CD25(low) GITR(+) cells represent a distinct Treg subpopulation.

Bianchini R ，Bistoni O ，Alunno A ，Petrillo MG ，Ronchetti S ，Sportoletti P ，Bocci EB ，Nocentini G ，Gerli R ，Riccardi C ... -  《-》

Stimulation of α7 nicotinic acetylcholine receptor by nicotine increases suppressive capacity of naturally occurring CD4+CD25+ regulatory T cells in mice in vitro.

Wang DW ，Zhou RB ，Yao YM ，Zhu XM ，Yin YM ，Zhao GJ ，Dong N ，Sheng ZY ... -  《-》

Dendritic cells partially abrogate the regulatory activity of CD4+CD25+ T cells present in the human peripheral blood.

Ahn JS ，Krishnadas DK ，Agrawal B 《INTERNATIONAL IMMUNOLOGY》

Forced overexpression of either of the two common human Foxp3 isoforms can induce regulatory T cells from CD4(+)CD25(-) cells.

Aarts-Riemens T ，Emmelot ME ，Verdonck LF ，Mutis T ... -  《EUROPEAN JOURNAL OF IMMUNOLOGY》

Identification and characterization of Foxp3(+) gammadelta T cells in mouse and human.

Kang N ，Tang L ，Li X ，Wu D ，Li W ，Chen X ，Cui L ，Ba D ，He W ... -  《-》