title: FOXN1 mutation abrogates prenatal T-cell development in humans.
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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, 'Federico II' University, Via Pansini, 5, Naples 80131, Italy. pignata@unina.it
authors.forename: I
authors.initials: I
authors.lastname: Vigliano
authors.forename: M
authors.initials: M
authors.lastname: Gorrese
authors.forename: A
authors.initials: A
authors.lastname: Fusco
authors.forename: L
authors.initials: L
authors.lastname: Vitiello
authors.forename: S
authors.initials: S
authors.lastname: Amorosi
authors.forename: L
authors.initials: L
authors.lastname: Panico
authors.forename: M V
authors.initials: MV
authors.lastname: Ursini
authors.forename: G
authors.initials: G
authors.lastname: Calcagno
authors.forename: L
authors.initials: L
authors.lastname: Racioppi
authors.forename: L
authors.initials: L
authors.lastname: Del Vecchio
authors.forename: C
authors.initials: C
authors.lastname: Pignata
mesh_terms: D015704:CD4 Antigens / Q000235:genetics* / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics* / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D005260:Female; D005315:Fetal Diseases / Q000235:genetics / Q000276:immunology; D005333:Fetus / Q000196:embryology / Q000276:immunology / Q000503:physiopathology; D051858:Forkhead Transcription Factors / Q000235:genetics; D005817:Genetic Counseling; D006801:Humans; D018655:Lymphocyte Count; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology; D009154:Mutation / Q000276:immunology; D011247:Pregnancy; D011296:Prenatal Diagnosis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D016511:Severe Combined Immunodeficiency / Q000196:embryology / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D051858:Forkhead Transcription Factors; D016692:Receptors, Antigen, T-Cell, gamma-delta; C090140:Whn protein