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Dok-1 overexpression promotes development of γδ natural killer T cells.

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.
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Contributor : Charles M. Dozois Connect in order to contact the contributor
Submitted on : Tuesday, April 30, 2013 - 4:10:38 AM
Last modification on : Wednesday, February 10, 2021 - 10:10:02 AM




Gilles Besin, Mitra Yousefi, Ingrid Saba, Roscoe Klinck, Pier Paolo Pandolfi, et al.. Dok-1 overexpression promotes development of γδ natural killer T cells.. European Journal of Immunology, 2012, 42 (9), pp.2491-504. ⟨10.1002/eji.201242421⟩. ⟨pasteur-00819061⟩



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