Role of the gut as a primary lymphoid organ

The TCR-αβ/γδ CD8αα intraepithelial T lymphocytes (T-IEL) located in the gut mucosa of the small intestine are an abundant population believed to have a major role in ensuring the integrity of the gut wall. Here, we describe their unique characteristics and the controversies regarding the origin and differentiation of these T-IELs. We show how accumulated experimental evidence has finally arrived at a unifying concept, which demonstrates that these cells originate from early thymus precursors that have not yet undergone TCR rearrangement and TCR-αβ/γδ commitment. These precursors colonize the gut lamina propria during the perinatal period and complete rearrangements and TCR-αβ/γδ commitment while migrating to the epithelium. Therefore, the gut epithelium, which shares the same embryonic origin as the thymus epithelium, behaves as a primary lymphoid organ responsible for the differentiation of a major local T cell set.