Extrathymic T-cell development is a topic of considerable interest and
debate, with important implications for the mechanisms of T-cell matu
ration and repertoire selection. Recent evidence has suggested that in
traepithelial T lymphocytes (IELs) of the small intestine can mature a
nd undergo selection in the absence of a thymus. However, IEL precurso
rs are present in the thymus and IEL development is know to be influen
ced by the thymus. Here, Leo Lefrancois and Lynn Puddington discuss th
ese data and suggest that the differentiation pathway of IEL precursor
s is dependent on whether or not a thymus is present.