T lymphocytes in the intestinal mucosa: defense and tolerance

Although lymphocytes are known to circulate throughout lymphoid tissues and blood, they also establish residency in nonlymphoid organs, most prominently in barrier tissues, such as the intestines. The adaptation of T lymphocytes to intestinal environments requires constant discrimination between natural stimulation from commensal flora and food and pathogens that need to be cleared. Genetic variations that cause a defective defense or a break in tolerance along with environmental cues, such as infection or imbalances in the gut microbiota known as dysbiosis, can trigger several immune disorders via the activation of T lymphocytes in the intestines. Elucidation of the immune mechanisms that distinguish between commensal flora and pathogenic organisms may reveal therapeutic targets for the prevention or modulation of inflammatory diseases and boost the efficacy of cancer immunotherapy. In this review, we discuss the development and adaptation of T lymphocytes in the intestine, how these cells protect the host against pathogenic infections while tolerating food antigens and commensal microbiota, and the potential implications of targeting these cells for disease management and therapeutics.