Deciphering the factors determining the differentiation of autoreactive thymocytes into regulatory T cells

Abstract

Regulatory T cells (Tregs) generation mechanisms. Tregs can be originated from the thymus upon self-antigens stimulation (tTregs) or in specialized peripheral tissues (pTregs) from naïve CD4 + T cells upon foreign antigenic stimulation. During thymic selection, anti-apoptotic Bcl-2 expression at late stages prevents clonal deletion of thymocytes and enhances the upregulation of cReI. Treg generation requires a disruption of agonist signalling by TGFβ, consequently leading to induce Foxo1 and Foxp3 expression. When agonist signalling persists, CD25 + precursors differentiate into T effector (Teff) cells, which produce IL-2 necessary for the last step of tTreg maturation. Function of Teff cells is regulated by both tTregs and pTregs, which prevents pathological immune responses and controls inflammation.