Interleukin-7 matures suppressive CD127(+) forkhead box P3 (FoxP3) (+) T cells into CD127(-) CD25(high) FoxP3 (+) regulatory T cells

Abstract

Summary We have identified a novel interleukin (IL)-7-responsive T cell population [forkhead box P3 (FoxP3+) CD4+ CD25+ CD127+] that is comparably functionally suppressive to conventional FoxP3+ CD4+ CD25+ regulatory T cells (Tregs). Although IL-2 is the most critical cytokine for thymic development of FoxP3+ Tregs, in the periphery other cytokines can be compensatory. CD25+ CD127+ T cells treated with IL-7 phenotypically ‘matured’ into the known ‘classical’ FoxP3+ CD4+ CD25highCD127- FoxP3+ Tregs. In freshly isolated splenocytes, the highest level of FoxP3 expression was found in CD127+ CD25+ T cells when compared with CD127- CD25+ or CD127+ CD25- cells. IL-7 treatment of CD4+ CD25+ T cells induced an increase in the accumulation of FoxP3 in the nucleus in vitro. IL-7-mediated CD25 cell surface up-regulation was accompanied by a concurrent down-regulation of CD127 in vitro. IL-7 treatment of the CD127+ CD25+ FoxP3+ cells also resulted in up-regulation of cytotoxic T lymphocyte antigen 4 without any changes in CD45RA at the cell surface. Collectively, these data support emerging evidence that FoxP3+ T cells expressing CD127 are comparably functionally suppressive to CD25+ CD127- FoxP3+ T cells. This IL-7-sensitive regulation of FoxP3+ Treg phenotype could underlie one peripheral non-IL-2-dependent compensatory mechanism of Treg survival and functional activity, particularly for adaptive Tregs in the control of autoimmunity or suppression of activated effector T cells.

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