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Dok-1 overexpression promotes development of γδ natural killer T cells
Gilles Besin1, Mitra Yousefi, Ingrid Saba
1Institut National de la Recherche Scientifique-Institut Armand-Frappier, Université du Québec, Laval, Canada.
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.
Insights
Dok-1 overexpression in T cells hinders development and promotes specific innate-like T cell populations. This study reveals Dok-1
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Dok-1 and Dok-2 are T cell-expressed Dok family members.
- Evidence suggests Dok proteins negatively regulate T cell signaling.
Purpose of the Study:
- To investigate the role of Dok-1 in T cell development.
- To define Dok-1's function in thymocyte and peripheral T cell regulation.
Main Methods:
- Generated transgenic mice overexpressing Dok-1 in T cells.
- Analyzed thymocyte development stages (CD4(-)CD8(-) to CD4(+)CD8(+)).
- Characterized specific T cell subsets (γδ T cells, CD8(+) T cells).
Main Results:
- Dok-1 overexpression impeded the CD4(-)CD8(-) to CD4(+)CD8(+) transition.
- Observed expansion of PLZF-expressing Vγ1.1(+)Vδ6.3(+) γδ T cells with innate characteristics (IL-4 production, SAP-dependent).
- Identified an innate-like CD8(+) T cell population expressing Eomesodermin.
Conclusions:
- Dok-1 plays a novel regulatory role in thymic differentiation.
- Dok-1 is crucial for the development of specific γδ T cell populations.
- Dok-1 influences the generation of innate-like CD8(+) T cells.
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