Development and function of IL-10-secreting regulatory T cells: Comparison with naturally occurring CD4+CD25+ regulatory T cells

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. Thus, these different regulatory populations may have different roles at different stages of the immune response.