IL-10-Secreting Regulatory T Cells Do Not Express Foxp3 but Have Comparable Regulatory Function to Naturally Occurring CD4+CD25+ Regulatory T Cells

TLDR

Regulatory T cells control immune responses to self and nonself antigens, but the relationship between antigen‑driven IL‑10‑secreting TReg and naturally occurring CD4+CD25+ TReg remains unclear. Mouse IL‑10‑secreting TReg lack Foxp3 yet suppress CD4+CD25− T cell proliferation as efficiently as CD4+CD25+ TReg through an IL‑10‑independent, IL‑2‑sensitive mechanism, indicating that Foxp3 is not required for regulatory activity and that the two subsets may arise from distinct origins.

Abstract

Abstract Regulatory T cells (TReg) control immune responses to self and nonself Ags. The relationship between Ag-driven IL-10-secreting TReg (IL-10-TReg) and naturally occurring CD4+CD25+ TReg is as yet unclear. We show that mouse IL-10-TReg obtained using either in vitro or in vivo regimens of antigenic stimulation did not express the CD4+CD25+ TReg-associated transcription factor Foxp3. However, despite the absence of Foxp3 expression, homogeneous populations of IL-10-TReg inhibited the in vitro proliferation of CD4+CD25− T cells with a similar efficiency to that of CD4+CD25+ TReg. This inhibition of T cell proliferation by IL-10-TReg was achieved through an IL-10-independent mechanism as seen for CD4+CD25+ TReg and was overcome by exogenous IL-2. Both IL-10-TReg and CD4+CD25+ TReg were similar in that they produced little to no IL-2. These data show that Foxp3 expression is not a prerequisite for IL-10-TReg activity in vitro or in vivo, and suggest that IL-10-TReg and naturally occurring CD4+CD25+ TReg may have distinct origins.