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.
- Severe combined immunodeficiency
- T-cell development
- Clinical genetics, Immunology (including allergy)
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Funding This work was supported by Grant Regione Campania, Legge 5/2005.
Competing interests None.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.