Extrathymic intestinal T-cell development: virtual reality?

Extrathymic T-cell development is a topic of considerable interest and debate, with important implications for the mechanisms of T-cell maturation and repertoire selection. Recent evidence has suggested that intraepithelial T lymphocytes (IELs) of the small intestine can mature and undergo selection in the absence of a thymus. However, IEL precursors are present in the thymus and IEL development is known to be influenced by the thymus. Here, Leo Lefrançois and Lynn Puddington discuss these data and suggest that the differentiation pathway of IEL precursors is dependent on whether or not a thymus is present.