Development of thymic Foxp3(+) regulatory T cells: TGF-beta matters

作者：Chen WanJun^*; Konkel Joanne E

来源：European Journal of Immunology, 2015, 45(4): 958-965.

DOI：10.1002/eji.201444999

• Apoptosis
• Foxp3
• IL-2
• Thymic Treg cells
• TGF- beta

CD4(+) regulatory T cells expressing the transcription factor Foxp3 can be generated in the thymus (tTreg cells), but the cellular and molecular pathways driving their development remain incompletely understood. TGF- is essential for the generation of Foxp3(+) Treg cells converted from peripheral naive CD4(+) T cells (pTreg cells), yet a role for TGF- in tTreg-cell development was initially refuted. Nevertheless, recent studies have unmasked a requirement for TGF- in the generation of tTreg cells. Experimental evidence reveals that TGF-in the context of TCR stimulation induces Foxp3 gene transcription in thymic Treg precursors, CD4(+)CD8(-)CD25(-) semimature and mature single-positive thymocytes. Intriguingly, thymic apoptosis was found to be intrinsically linked to the generation of tTreg cells, as apoptosis induced expression of TGF- intrathymically. In this short review, we will highlight key data, discuss the experimental evidence and propose a modified model of tTreg-cell development involving TGF-. We will also outline the remaining unresolved questions concerning generation of thymic Foxp3(+) Treg cells and provide our personal perspectives on the mechanisms controlling tTreg-cell development.

• 出版日期2015-4
• 单位NIH