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The intestinal mucosa represents a large surface area that is in contact with an immense antigenic load. The immune system associated with the intestinal mucosa needs to distinguish between innocuous food antigens, commensal microorganisms, and pathogenic microorganisms, without triggering an exaggerated immune response that may lead to excessive inflammation and/or development of inflammatory bowel disease. The thymus leukemia (TL) antigen and CD8αα are interacting surface molecules that are expressed at the frontline of the mucosal immune system: TL is expressed in intestinal epithelial cells (IEC) whereas CD8αα is expressed in lymphocytes, known as intraepithelial lymphocytes, that reside in between the IEC. In this review we discuss the significance of the interaction between TL and CD8αα in mucosal immunity during health and disease.
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