FOXN1 mutation abrogates prenatal T-cell development in humans
Résumé
The transcription factor FOXN1 is implicated in the differentiation of thymic and skin epithelial cells and its alterations are responsible for the Nude/SCID phenotype. During a genetic counseling program offered to couples at risk in the community where a high frequency of mutated FOXN1 has been documented, the identification of a human FOXN1-/- fetus gave the unique opportunity to study T-cell development in utero. A total blockage of CD4+ T-cell maturation and a severe impairment of CD8+ cells were documented. The evaluation of the variable-domain β-chain (Vβ) families' usage among T lymphocytes revealed that the generation of TCR diversity occurred at some extent in the FOXN1-/- fetus, although it was impaired compared to the control. A few non-functional CD8+ cells, mostly bearing TCRγδ in the absence of CD3 were found. 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, thus implying a FOXN1-independent lymphopoiesis.
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