Abstract
Thymocytes and thymic epithelial cell (TEC) cross-talk is crucial to preserve thymic architecture and function, including maturation of TECs and dendritic cells, and induction of mechanisms of central tolerance.We have analyzed thymic maturation and organization in 9 infants with various genetic defects leading to complete or partial block in T-cell development. Profound abnormalities of TEC differentiation (with lack of AIRE expression) and severe reduction of thymic dendritic cells were identified in patients with Tnegative severe combined immunodeficiency, reticular dysgenesis, and Omenn syndrome. The latter also showed virtual absence of thymic Foxp3+ T cells. In contrast, an IL2RG-R222C hypomorphic mutation permissive for T-cell development allowed for TEC maturation, AIRE expression, and Foxp3+ T cells. Our data provide evidence that severe defects of thymopoiesis impinge on TEC homeostasis and may affect deletional and nondeletional mechanisms of central tolerance, thus favoring immune dysreactive manifestations, as in Omenn syndrome.
| Original language | English |
|---|---|
| Pages (from-to) | 105-108 |
| Number of pages | 4 |
| Journal | Blood |
| Volume | 114 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2009 |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
Early defects in human T-cell development severely affect distribution and maturation of thymic stromal cells : Possible implications for the pathophysiology of Omenn syndrome. / Poliani, Pietro Luigi; Facchetti, Fabio; Ravanini, Maria; Gennery, Andrew Richard; Villa, Anna; Roifman, Chaim M.; Notarangelo, Luigi D.
In: Blood, Vol. 114, No. 1, 2009, p. 105-108.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Early defects in human T-cell development severely affect distribution and maturation of thymic stromal cells
T2 - Possible implications for the pathophysiology of Omenn syndrome
AU - Poliani, Pietro Luigi
AU - Facchetti, Fabio
AU - Ravanini, Maria
AU - Gennery, Andrew Richard
AU - Villa, Anna
AU - Roifman, Chaim M.
AU - Notarangelo, Luigi D.
PY - 2009
Y1 - 2009
N2 - Thymocytes and thymic epithelial cell (TEC) cross-talk is crucial to preserve thymic architecture and function, including maturation of TECs and dendritic cells, and induction of mechanisms of central tolerance.We have analyzed thymic maturation and organization in 9 infants with various genetic defects leading to complete or partial block in T-cell development. Profound abnormalities of TEC differentiation (with lack of AIRE expression) and severe reduction of thymic dendritic cells were identified in patients with Tnegative severe combined immunodeficiency, reticular dysgenesis, and Omenn syndrome. The latter also showed virtual absence of thymic Foxp3+ T cells. In contrast, an IL2RG-R222C hypomorphic mutation permissive for T-cell development allowed for TEC maturation, AIRE expression, and Foxp3+ T cells. Our data provide evidence that severe defects of thymopoiesis impinge on TEC homeostasis and may affect deletional and nondeletional mechanisms of central tolerance, thus favoring immune dysreactive manifestations, as in Omenn syndrome.
AB - Thymocytes and thymic epithelial cell (TEC) cross-talk is crucial to preserve thymic architecture and function, including maturation of TECs and dendritic cells, and induction of mechanisms of central tolerance.We have analyzed thymic maturation and organization in 9 infants with various genetic defects leading to complete or partial block in T-cell development. Profound abnormalities of TEC differentiation (with lack of AIRE expression) and severe reduction of thymic dendritic cells were identified in patients with Tnegative severe combined immunodeficiency, reticular dysgenesis, and Omenn syndrome. The latter also showed virtual absence of thymic Foxp3+ T cells. In contrast, an IL2RG-R222C hypomorphic mutation permissive for T-cell development allowed for TEC maturation, AIRE expression, and Foxp3+ T cells. Our data provide evidence that severe defects of thymopoiesis impinge on TEC homeostasis and may affect deletional and nondeletional mechanisms of central tolerance, thus favoring immune dysreactive manifestations, as in Omenn syndrome.
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U2 - 10.1182/blood-2009-03-211029
DO - 10.1182/blood-2009-03-211029
M3 - Article
VL - 114
SP - 105
EP - 108
JO - Blood
JF - Blood
SN - 0006-4971
IS - 1
ER -