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.
FOXN1 mutation abrogates prenatal T-cell development in humans
Calcagno, G.;
2011-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.