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. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.