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 (IL-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.