101. Gab3 Plays an Essential Role in CD8 +T-Cell Expansion through Regulating IL-2-Mediated Activation of PI3K/AKT/mTOR and Erk/FoxO Pathways
- Author
-
Fu, Guoping, Zheng, Yongwei, Xin, Gang, Wang, Zhengqi, Bunting, Kevin D., Cui, Weiguo, Salomon, Arthur, and Wen, Renren
- Abstract
Grb2-associated binding protein 3 (Gab3) is a member of the Gab family of scaffolding proteins. Its role in T cells is largely unknown. In the current study, we investigated its in vivo function in CD8 +T cells using the lymphocytic choriomeningitis virus (LCMV) Armstrong infection model. We created BM chimera mice with a specific deficiency of Gab3 in CD8 +T cells. This was achieved by transplanting a mixture of BM cells obtained from CD8-deficient mice and Gab3-deficient (Gab3 -/-) mice (1)into lethally irradiated CD45.1 mice. The control chimera mice were lethally irradiated CD45.1 mice transplanted with a mixture of BM cells from CD8-deficient mice and WT mice. Twelve weeks after the BM transplantation, the Gab3 -/-and control BM chimera mice were infected with Armstrong. On day eight following infection, Gab3 -/-CD8 +T cells exhibited reduced expansion compared to WT CD8 +T cells. Importantly, Gab3 -/-LCMV antigen specific CD8 +T cells, GP33 +and NP396 +CD8 +T cells, were significantly reduced compared to their WT counterparts. Furthermore, CD8 +T cells in Gab3 -/-BM chimera mice showed significant increase of apoptosis compared to that in WT BM chimera mice following LCMV infection.
- Published
- 2023
- Full Text
- View/download PDF