FOXN1 mutation abrogates prenatal T-cell development in humans

Results Total blockage of CD4(+) T cell maturation and severe impairment of CD8(+) cells were documented. Evaluation of the variable-domain beta-chain (V beta) 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 TCR gamma delta in the absence of CD3, were found.

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.