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

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