Inhibition of clonal expansion by Foxp3 expression as a mechanism of controlled T-cell responses and autoimmune disease.

摘要

The essential role of the transcription factor Foxp3 in the development and function of Treg has been well documented. The role of Foxp3 in non-Treg, however, is not fully understood. Emerging evidence indicates that Foxp3 expression is not confined to CD4+CD25+ Treg. The present study shows that in Foxp3 transgenic (Foxp3-Tg) mice, in which the transgene is driven by the lck distal promoter, CD4+CD25- T cells that express the Foxp3 transgene do not upregulate the expression of CD25-, GITR, or CTLA-4, and do not have suppressive function; however, the Foxp3-Tg+CD4+CD25- T cells exhibit significantly reduced proliferative response to TCR engagement. Foxp3-Tg mice are resistant to collagen-induced arthritis via reduced cellular proliferation of activated T cells. These findings indicate that Foxp3 upregulation in activated non-Treg may be a mechanism to suppress immune responses by reduced clonal expansion of activated T cells.