Dok-1 overexpression promotes development of γδ natural killer T cells.
Eur J Immunol
; 42(9): 2491-504, 2012 Sep.
Article
em En
| MEDLINE
| ID: mdl-22736313
ABSTRACT
In T cells, two members of the Dok family, Dok-1 and Dok-2, are predominantly expressed. Recent evidence suggests that they play a negative role in T-cell signaling. In order to define whether Dok proteins regulate T-cell development, we have generated transgenic mice overexpressing Dok-1 in thymocytes and peripheral T cells. We show that overexpression of Dok-1 retards the transition from the CD4(-) CD8(-) to CD4(+) CD8(+) stage. Moreover, there is a specific expansion of PLZF-expressing Vγ1.1(+) Vδ6.3(+) T cells. This subset of γδ T cells acquires innate characteristics including rapid IL-4 production following stimulation and requiring SLAM-associated adaptor protein (SAP) for their development. Moreover, Dok-1 overexpression promotes the generation of an innate-like CD8(+) T-cell population that expresses Eomesodermin. Altogether, these findings identify a novel role for Dok-1 in the regulation of thymic differentiation and in particular, in the development of PLZF(+) γδ T cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Linfócitos T CD4-Positivos
/
Proteínas de Ligação a RNA
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Receptores de Antígenos de Linfócitos T gama-delta
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Linfócitos T CD8-Positivos
/
Proteínas de Ligação a DNA
/
Células T Matadoras Naturais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Canadá