FOXN1 mutation abrogates prenatal T-cell development in humans.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Vigliano, I; Gorrese, M; Fusco, A; Vitiello, L; Amorosi, S; Panico, L; Ursini, MV; Calcagno, G; Racioppi, L; Del Vecchio, L; Pignata, C

Published Date

  • June 2011

Published In

Volume / Issue

  • 48 / 6

Start / End Page

  • 413 - 416

PubMed ID

  • 21507891

Electronic International Standard Serial Number (EISSN)

  • 1468-6244

Digital Object Identifier (DOI)

  • 10.1136/jmg.2011.089532


  • eng

Conference Location

  • England