Increased CD127 expression on activated FOXP3⁺CD4⁺ regulatory T cells

Abstract

Regulatory T cells (Treg) are commonly identified by CD25 (IL-2Ra) surface expression and/or intracellular expression of the FOXP3 transcription factor. In addition, Treg are also characterized by low CD127 (IL-7Ra) expression when compared to conventional T cells and their biology in the periphery is considered essentially independent of IL-7. We further investigated CD127 expression on Treg and we demonstrated differential CD127 expression depending on Treg subsets considered. Notably, we observed high CD127 expression on inducible costimulatory molecule (ICOS)-and CD103-expressing Treg subsets. Since these two markers reflect activation status, we addressed whether Treg activation modulated CD127 expression. We demonstrated that in contrast to conventional T cells, Treg significantly upregulated CD127 expression during in vitro and in vivo activation using adoptive transfer and contact dermatitis models. High CD127 expression on Treg was also predominantly detected ex vivo in some specific sites, notably bone marrow and skin. Importantly, higher CD127 expression on Treg correlated with higher phosphorylation of STAT5 upon IL-7 exposure. High CD127 expression on Treg also provided survival advantage upon in vitro incubation with IL-7. We thus demonstrated that low CD127 expression is not an intrinsic characteristic of Treg and we identified activated Treg as a potential target of endogenous or therapeutic IL-7.

Lymphocytes in obesity-related adipose tissue inflammation

“…One possible explanation for the discrepancies in human studies could be that FOXP3 expression is variable in human Tregs. This suggests that additional Treg markers, such as the low expression of CD127 in these cells, may need to be added to their analysis [57,58] to give a true reflection of the levels of this important T cell subpopulation in human WAT.…”

Tumor-Infiltrating Regulatory T Cells: Phenotype, Role, Mechanism of Expansion In Situ and Clinical Significance

“…absence of its expression) is not an ideal biomarker for the identification of Tregs, because a fraction of early-activated Teff cells are also CD25 + FOXP3 + C-D127 low/− and thus are indistinguishable from Tregs [11]. Conversely, it has been shown in mice that CD127 is also highly expressed on Tregs upon in vitro and in vivo activation and on fraction of Tregs located in tissues [12].…”

Unravelling the molecular basis for regulatory T‐cell plasticity and loss of function in disease

“…More recently, a search for cell surface surrogates of FOXP3 (FOXP3 cannot be used to isolate viable Treg as it requires intracellular staining) has revealed that reduced expression of the IL7 receptor (CD127) is also a hallmark of the human Treg phenotype 7, 8. It has been reported that CD127 is not selective for mouse Treg, as activated murine Treg express CD127 strongly 9. The differential expression of cytokine receptors on Treg may be important in restricting survival or function as, for example, mature human Treg are dependent on exogenous IL2, but not on IL7.…”