Details

Autor(en) / Beteiligte

• Laroche-Lefebvre, Constance
• Yousefi, Mitra
• Daudelin, Jean-François
• Charpentier, Tania
• Tarrab, Esther
• Klinck, Roscoe
• Lamarre, Alain
• Labrecque, Nathalie
• Stäger, Simona
• Duplay, Pascale

Titel

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

Ist Teil von

• The Journal of immunology (1950), 2016-11, Vol.197 (9), p.3618-3627

Ort / Verlag

United States: Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.