Research ArticleINFLAMMATORY BOWEL DISEASE

CD4+ T cell activation and concomitant mTOR metabolic inhibition can ablate microbiota-specific memory cells and prevent colitis

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Science Immunology  11 Dec 2020:
Vol. 5, Issue 54, eabc6373
DOI: 10.1126/sciimmunol.abc6373

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Eradicating microbiota-reactive effector T cells

Dysfunctional CD4+ T cell responses to gut microbiota antigens are the prime driver of inflammatory bowel disease. Patients with Crohn’s disease often exhibit both antibody and T cell responses targeting antigens from gut bacteria, especially flagellins. Zhao et al. developed a two-pronged strategy to weed out flagellin-reactive CD4+ T cells. Combined treatment using a metabolic inhibitor blocking the mTOR complex and induced T cell activation with an engineered peptide including flagellin epitopes achieved ablation of memory T cells in mouse models of colitis. The same combined approach also enabled purging of pathogenic T cells found in the blood of patients with Crohn’s disease. These findings support moving this line of investigation into human trials aimed at selective ablation of effector T cells causing Crohn’s disease.

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