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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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