That regulatory T cells can change their phenotypes has been shown in mouse models of atherosclerosis and other autoimmune diseases. We suspected that this phenomenon would also be true in humans. To test this hypothesis, we developed a strategy to identify human ‘exTreg’ cells and found that they express a cytotoxic transcriptome.
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Wolf, D. et al. Pathogenic autoimmunity in atherosclerosis evolves from initially protective apolipoprotein B100-reactive CD4+ T-regulatory cells. Circulation 142, 1279–1293 (2020). This paper shows how the transcriptomes of CD4+ T cells that recognize an atherosclerosis-specific antigen diverge from Treg cell transcriptomes.
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Saigusa, R. et al. Single cell transcriptomics and TCR reconstruction reveal CD4 T cell response to MHC-II-restricted APOB epitope in human cardiovascular disease. Nat. Cardiovasc. Res. 1, 462–475 (2022). This paper shows that adoptive transfer of exTreg cells into mice increases producion of the pro-inflammatory cytokine IFNγ.
Bailey-Bucktrout, S. L. et al. Self-antigen-driven activation induces instability of regulatory T cells during an inflammatory autoimmune response. Immunity 39, 949–962 (2013). This paper first showed that only antigen-specific Treg cells become exTreg cells.
Sharma, M. D. et al. Reprogrammed Foxp3+ regulatory T cells provide essential help to support cross-presentation and CD8+ T cell priming in naive mice. Immunity 33, 942–954 (2010). This paper shows that Treg cells can evolve to help control cancer in mice.
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This is a summary of: Freuchet, A. et al. Identification of human exTreg cells as CD16+CD56+ cytotoxic CD4+ T cells. Nat. Immunol. https://doi.org/10.1038/s41590-023-01589-9 (2023).
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Human regulatory T cells turn into cytotoxic ‘exTreg’ cells in atherosclerosis. Nat Immunol 24, 1614–1615 (2023). https://doi.org/10.1038/s41590-023-01629-4