Journal article
Phosphatidylinositol 3-Kinase p110δ Isoform Regulates CD8+ T Cell Responses during Acute Viral and Intracellular Bacterial Infections
The Journal of immunology (1950), v 196(3), pp 1186-1198
01 Feb 2016
PMID: 26740110
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The p110δ isoform of PI3K is known to play an important role in immunity, yet its contribution to 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.
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Details
- Title
- Phosphatidylinositol 3-Kinase p110δ Isoform Regulates CD8+ T Cell Responses during Acute Viral and Intracellular Bacterial Infections
- Creators
- Donald T Gracias - Drexel UniversityAlina C Boesteanu - Drexel UniversityJoseph A Fraietta - Drexel UniversityJennifer L Hope - Drexel UniversityAlison J Carey - Drexel UniversityYvonne M Mueller - Drexel UniversityOmkar U Kawalekar - University of PennsylvaniaAdam J Fike - Drexel UniversityCarl H June - University of PennsylvaniaPeter D Katsikis - Drexel University
- Publication Details
- The Journal of immunology (1950), v 196(3), pp 1186-1198
- Publisher
- American Association of Immunologists (AAI)
- Grant note
- R01 AI066215 / NIAID NIH HHS R01 AI66215 / NIAID NIH HHS T32 CA009140 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; Biology; Pediatrics
- Web of Science ID
- WOS:000368596600026
- Scopus ID
- 2-s2.0-84957694694
- Other Identifier
- 991019169792604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology