Murine thymic stromal lymphopoietin promotes the differentiation of regulatory T cells from thymic CD4(+)CD8(-)CD25(-) naive cells in a dendritic cell-independent manner

Abstract

Human thymic stromal lymphopoietin (TSLP) activates dendritic cells (DCs), which promote the proliferation and differentiation of CD4(+) T cells. However, murine TSLP (mTSLP) can act directly on CD4(+) T cells and bring about their differentiation. We studied the role of mTSLP in the generation of CD4(+)CD25(+)FoxP3(+) T cells from thymocytes. mTSLP promoted the differentiation of CD4(+) single-positive thymocytes into CD4(+)CD25(+)FoxP3(+) T cells. Although we cannot exclude an effect of TSLP mediated through DCs due to co- stimulatory effects, mTSLP appears to act directly on thymocytes. T- cell receptor and TSLP receptor signaling act synergistically on thymocytes to generate CD4(+)CD25(+) FoxP3(+) T cells. mTSLP may play an important role in maintaining immune tolerance by promoting the conversion of thymocytes into natural regulatory T cells via escape from negative selection.