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

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 (T regs ). Although IL‐2 is the most critical cytokine for thymic development of FoxP3 + T regs , in the periphery other cytokines can be compensatory. CD25 + CD127 + T cells treated with IL‐7 phenotypically ‘matured’ into the known ‘classical’ FoxP3 + CD4 + CD25 high CD127 ‐ FoxP3 + T regs . 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 + T reg phenotype could underlie one peripheral non‐IL‐2‐dependent compensatory mechanism of T reg survival and functional activity, particularly for adaptive T regs in the control of autoimmunity or suppression of activated effector T cells.