FOXP3 protects conventional human T cells from premature restimulation-induced cell death.

FOXP3 protects conventional human T cells from premature restimulation-induced cell death. Cell Mol Immunol. 2019 Oct 28;: Authors: Voss K, Lake C, Luthers CR, Lott NM, Dorjbal B, Arjunaraja S, Bauman BM, Soltis AR, Sukumar G, Dalgard CL, Snow AL Abstract The adaptive immune response relies on specific apoptotic programs to maintain homeostasis. Conventional effector T cell (Tcon) expansion is constrained by both forkhead box P3 (FOXP3)+-regulatory T cells (Tregs) and restimulation-induced cell death (RICD), a propriocidal apoptosis pathway triggered by repeated stimulation through the T-cell receptor (TCR). Constitutive FOXP3 expression protects Tregs from RICD by suppressing SLAM-associated protein (SAP), a key adaptor protein that amplifies TCR signaling strength. The role of transient FOXP3 induction in activated human CD4 and CD8 Tcons remains unresolved, but its expression is inversely correlated with acquired RICD sensitivity. Here, we describe a novel role for FOXP3 in protecting human Tcons from premature RICD during expansion. Unlike FOXP3-mediated protection from RICD in Tregs, FOXP3 protects Tcons through a distinct mechanism requiring de novo transcription that does not require SAP suppression. Transcriptome profiling and functional analyses of expanding Tcons revealed that FOXP3 enhances expression of the SLAM family receptor CD48, which in turn sustains basal autophagy and suppresses pro-apoptotic p53 signaling. Both C...
Source: Cellular and Molecular Immunology - Category: Molecular Biology Authors: Tags: Cell Mol Immunol Source Type: research