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FOXN1 mutation abrogates prenatal T-cell development in humans
  1. I Vigliano1,
  2. M Gorrese2,
  3. A Fusco1,
  4. L Vitiello3,
  5. S Amorosi1,
  6. L Panico4,
  7. M V Ursini5,
  8. G Calcagno2,
  9. L Racioppi3,
  10. L Del Vecchio2,
  11. C Pignata1
  1. 1Department of Pediatrics, ‘Federico II’ University, Naples, Italy
  2. 2Department of Biochemistry and Medical Biotechnology-CEINGE, ‘Federico II’ University, Naples, Italy
  3. 3Department of Cellular and Molecular Biology and Pathology, ‘Federico II’ University, Naples, Italy
  4. 4Unit of Pathology, National Relevance Hospital ‘S G Moscati’, Avellino, Italy
  5. 5Institute of Genetics and Biophysics ‘A Buzzati-Traverso’, CNR, Naples, Italy
  1. Correspondence to Claudio Pignata, Department of Pediatrics, ‘Federico II’ University, Via Pansini, 5, Naples 80131, Italy; pignata{at}


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
  • FOXN1
  • 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.