Dok-1 and Dok-2 Regulate the Formation of Memory CD8+ T Cells
| Autor: | Pascale Duplay, Tania Charpentier, Mitra Yousefi, Simona Stäger, Jean-François Daudelin, Roscoe Klinck, Esther Tarrab, Alain Lamarre, Constance Laroche-Lefebvre, Nathalie Labrecque |
|---|---|
| Přispěvatelé: | Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Maisonneuve-Rosemont Hospital Research Center, Université de Sherbrooke (UdeS) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell Survival T cell [SDV]Life Sciences [q-bio] Receptors Antigen T-Cell alpha-beta Immunology Biology CD8-Positive T-Lymphocytes Lymphocyte Activation 03 medical and health sciences Interleukin 21 Mice 0302 clinical medicine medicine Vaccinia Immunology and Allergy Cytotoxic T cell Animals IL-2 receptor Antigen-presenting cell Cells Cultured Adaptor Proteins Signal Transducing Mice Knockout ZAP70 RNA-Binding Proteins Cell Differentiation Natural killer T cell Phosphoproteins Cell biology DNA-Binding Proteins Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Virus Diseases Immunologic Memory CD8 030215 immunology Signal Transduction |
| Zdroj: | Journal of Immunology 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⟩ |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|