The thymic medulla is required for Foxp3+ regulatory but not conventional CD4+ thymocyte development.
J Exp Med
; 210(4): 675-81, 2013 Apr 08.
Article
en En
| MEDLINE
| ID: mdl-23530124
ABSTRACT
A key role of the thymic medulla is to negatively select autoreactive CD4(+) and CD8(+) thymocytes, a process important for T cell tolerance induction. However, the involvement of the thymic medulla in other aspects of αß T cell development, including the generation of Foxp3(+) natural regulatory T cells (nTreg cells) and the continued maturation of positively selected conventional αß T cells, is unclear. We show that newly generated conventional CD69(+)Qa2(-) CD4 single-positive thymocytes mature to the late CD69(-)Qa2(+) stage in the absence of RelB-dependent medullary thymic epithelial cells (mTECs). Furthermore, an increasing ability to continue maturation extrathymically is observed within the CD69(+)CCR7(-/lo)CCR9(+) subset of conventional SP4 thymocytes, providing evidence for an independence from medullary support by the earliest stages after positive selection. In contrast, Foxp3(+) nTreg cell development is medullary dependent, with mTECs fostering the generation of Foxp3(-)CD25(+) nTreg cell precursors at the CD69(+)CCR7(+)CCR9(-) stage. Our results demonstrate a differential requirement for the thymic medulla in relation to CD4 conventional and Foxp3(+) thymocyte lineages, in which an intact mTEC compartment is a prerequisite for Foxp3(+) nTreg cell development through the generation of Foxp3(-)CD25(+) nTreg cell precursors.
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Base de datos:
MEDLINE
Asunto principal:
Timo
/
Diferenciación Celular
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Linfocitos T Reguladores
/
Factores de Transcripción Forkhead
/
Timocitos
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2013
Tipo del documento:
Article
País de afiliación:
Reino Unido