期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 41, 期 8, 页码 2269-2278出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201040943
关键词
CD4(+) T lymphocytes; TNFR superfamily; Treg cell marker
类别
资金
- Italian Association for Cancer Research (AIRC) in Milan, Italy
- network Fondo per gli Investimenti della Ricerca di Base, (Italy) [RBPR05NWWC]
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-beta. 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-beta 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-beta. 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.
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