Phosphatidylinositol 3-Kinase p110δ Isoform Regulates CD8+ T Cell Responses during Acute Viral and Intracellular Bacterial Infections.
Phosphatidylinositol 3-Kinase p110δ Isoform Regulates CD8+ T Cell Responses during Acute Viral and Intracellular Bacterial Infections.
复制标题
DOI：
10.4049/jimmunol.1501890
复制
发表时间：
2016-02-01
期刊：
影响因子：
--
通讯作者：
Katsikis PD
中科院分区：
文献类型：
--
作者：
Gracias DT;Boesteanu AC;Fraietta JA;Hope JL;Carey AJ;Mueller YM;Kawalekar OU;Fike AJ;June CH;Katsikis PD
The p110δ isoform of phosphatidylinositol 3-kinase (PI3K) is known to play an important role in immunity, yet its contribution to Cytotoxic T lymphocyte (CTL) responses has not been fully elucidated. Using murine p110δ deficient CD8+ T cells, we demonstrated a critical role for the p110δ subunit in the generation of optimal primary and memory CD8+ T cell responses. This was demonstrated in both acute viral and intracellular bacterial infections in mice. We show that p110δ signaling is required for CD8+ T cell activation, proliferation and effector cytokine production. We provide evidence that the effects of p110δ signaling are mediated via Akt activation and through the regulation of TCR-activated oxidative phosphorylation and aerobic glycolysis. In light of recent clinical trials that employ drugs targeting p110δ in certain cancers and other diseases, our study suggests caution in using these drugs in patients, as they could potentially increase susceptibility to infectious diseases. These studies therefore reveal a novel and direct role for p110δ signaling in in vivo CD8+ T cell immunity to microbial pathogens.
