Dok-1 and Dok-2 Regulate the Formation of Memory CD8 + T Cells

Constance Laroche-Lefebvre 1 Mitra Yousefi 1 Jean-François Daudelin 2 Tania Charpentier 1 Esther Tarrab 1 Roscoe Klinck 3 Alain Lamarre 1 Nathalie Labrecque 2 Simona Stäger 1 Pascale Duplay 1
1 INRS-IAF - Institut Armand Frappier
2 Maisonneuve-Rosemont Hospital Research Center
3 Université de Sherbrooke [Sherbrooke]
Abstract : Diverse signals received by CD8+ T cells are integrated to achieve the required magnitude of cell expansion and the appropriate balance of effector/memory CD8+ T cell generation. Notably, the strength and nature of TCR signaling influence the differentiation and functional capacity of effector and memory CD8+ T cells. Dok-1 and Dok-2, the two members of the Dok family expressed in T cells, negatively regulate TCR signaling in vitro. However, the role of Dok proteins in modulating T cell function in vivo has not yet studied. We studied the function of Dok-1 and Dok-2 proteins in the regulation of the CD8+ T cell response to vaccinia virus infection. Comparison of responses to vaccinia virus expressing OVA peptide SIINFEKL by wild-type and Dok-1/2−/− CD8+ OT-I cells showed that the absence of Dok-1 and Dok-2 slightly reduced the magnitude of virus-specific effector CD8+ T cell expansion. This was not due to reduced proliferation or enhanced apoptosis of effector CD8+ T cells. Dok-1/2–deficient effector CD8+ T cells showed increased cell surface TCR expression following virus infection in vivo and increased expression of granzyme B and TNF upon stimulation with peptide Ag ex vivo. Finally, Dok-1/2–deficient effector CD8+ T had a severe defect in survival that resulted in impaired generation of memory CD8+ T cells. These results reveal the critical involvement of Dok-1 and Dok-2 in a negative-feedback loop that prevents overactivation of CD8+ T cells and promotes memory formation.
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Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2017, 197 (9), pp.3618 - 3627. 〈10.4049/jimmunol.1600385〉
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Contributeur : Michel Courcelles <>
Soumis le : mercredi 21 décembre 2016 - 16:39:05
Dernière modification le : lundi 8 octobre 2018 - 17:44:05

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Constance Laroche-Lefebvre, Mitra Yousefi, Jean-François Daudelin, Tania Charpentier, Esther Tarrab, et al.. Dok-1 and Dok-2 Regulate the Formation of Memory CD8 + T Cells. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2017, 197 (9), pp.3618 - 3627. 〈10.4049/jimmunol.1600385〉. 〈pasteur-01421153〉

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