TCR density in early iNKT cell precursors regulates agonist selection and subset differentiation in mice.
Eur J Immunol
; 49(6): 894-910, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30912587
ABSTRACT
It is established that iNKT cells are a cell type that require strong TCR signal for their proper development and represent a model for thymic agonist selection. The nature of the signal perceived by iNKT cells promoting their specification is not well understood. To address this question, we analyzed iNKT cell development in relevant TCR Vα14-Jα18 alpha chain transgenic mice (Vα14Tg). In CD4-Vα14Tg mice, where the transgene is driven by CD4 promoter, we identified a block in iNKT cell development at early developmental stages due to a reduced expression of key transcription factors accompanied with a reduced TCR expression levels. This indicates that TCR signal strength control iNKT cell differentiation. Importantly, we found in WT mice that early precursors of iNKT cells express higher TCR levels compared to positively selected precursors of mainstream T cells showing that TCR levels could contribute to the strength of iNKT cell TCR signaling. Overall, our study highlights TCR signal strength associated with a higher TCR density as an important regulator of iNKT cell lineage specification.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Subpopulações de Linfócitos T
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Receptores de Antígenos de Linfócitos T alfa-beta
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Células T Matadoras Naturais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
França