FOXN1 mutation abrogates prenatal T-cell development in humans.
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.
Duke Scholars
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Related Subject Headings
- Thymus Gland
- T-Lymphocytes
- Severe Combined Immunodeficiency
- Receptors, Antigen, T-Cell, gamma-delta
- Prenatal Diagnosis
- Pregnancy
- Mutation
- Lymphopoiesis
- Lymphocyte Count
- Humans
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Thymus Gland
- T-Lymphocytes
- Severe Combined Immunodeficiency
- Receptors, Antigen, T-Cell, gamma-delta
- Prenatal Diagnosis
- Pregnancy
- Mutation
- Lymphopoiesis
- Lymphocyte Count
- Humans