Dépôt numérique

Dok-1 overexpression promotes development of gammadelta natural killer T cells

Besin, Gilles; Yousefi, Mitra; Saba, Ingrid; Klinck, Roscoe; Pandolfi, Pier Paolo et Duplay, Pascale (2012). Dok-1 overexpression promotes development of gammadelta natural killer T cells European Journal of Immunology , vol. 42 , nº 9. pp. 2491-504. DOI: 10.1002/eji.201242421.

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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 Vgamma1.1(+) Vdelta6.3(+) T cells. This subset of gammadelta 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(+) gammadelta T cells.

Type de document: Article
Mots-clés libres: γδ T cell; Dok; PLZF; SAP; Thymocyte development
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 06 mars 2024 15:15
Dernière modification: 06 mars 2024 15:15
URI: https://espace.inrs.ca/id/eprint/13989

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