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 b-chain (Vb) 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 nonfunctional CD8+ cells, mostly bearing TCRγ δ 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.
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