Background The transcription factor FOXN1 is implicated in the differentiation of thymic and skin epithelial cells, and alterations in it are responsible for the Nude/SCID phenotype. During a genetic counselling programme offered to couples at risk in a community where a high frequency of mutated FOXN1 had been documented, the identification of a human FOXN1^−/− fetus gave the unique opportunity to study T cell development in utero.

Results Total blockage of CD4⁺ T cell maturation and severe impairment of CD8⁺ cells were documented. Evaluation of the variable-domain β-chain (Vβ) families' usage among T lymphocytes revealed that the generation of T cell receptor (TCR) diversity occurred to some extent in the FOXN1^−/− fetus, although it was impaired compared with the control. A few non-functional CD8⁺ cells, mostly bearing TCRγδ in the absence of CD3, were found.

Discussion FOXN1 is crucial for in utero T cell development in humans. The identification of a limited number of CD8⁺ cells suggests an extrathymic origin for these cells, implying FOXN1-independent lymphopoiesis.