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

摘要

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.