Dok-1 overexpression promotes development of γδ natural killer T cells.
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.
Institut National de la Recherche Scientifique-Institut Armand-Frappier, Université du Québec, Laval, Canada.
Gilles
G
Besin
Mitra
M
Yousefi
Ingrid
I
Saba
Roscoe
R
Klinck
Pier Paolo
PP
Pandolfi
Pascale
P
Duplay
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000378:metabolism*; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein
D004268:DNA-Binding Proteins; C489561:Dok1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; D010750:Phosphoproteins; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D016601:RNA-Binding Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C499569:Sh2d1a protein, mouse; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; C513267:Zbtb16 protein, mouse