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We previously showed that PP2A regulates the differentiation of CD4\n            <jats:sup>+<\/jats:sup>\n            T cells and the development of thymocytes. Nevertheless, its role in CD8\n            <jats:sup>+<\/jats:sup>\n            T cells remains elusive. By ablating the catalytic subunit \u03b1 (C\u03b1) of PP2A in CD8\n            <jats:sup>+<\/jats:sup>\n            T cells, we revealed the essential role of PP2A in promoting the effector functions of CD8\n            <jats:sup>+<\/jats:sup>\n            T cells. Notably, PP2A C\u03b1-deficient CD8\n            <jats:sup>+<\/jats:sup>\n            T cells exhibit reduced proliferation and decreased cytokine production upon stimulation in\u00a0vitro. In\u00a0vivo, mice lacking PP2A C\u03b1 in T cells displayed defective immune responses against lymphocytic choriomeningitis virus infection, associated with reduced CD8\n            <jats:sup>+<\/jats:sup>\n            T cell expansion and decreased cytokine production. Consistently, the ablation of the PP2A C\u03b1 subunit in CD8\n            <jats:sup>+<\/jats:sup>\n            T cells results in attenuated antitumor activity in mice. There is a notable decrease in the infiltration of PP2A C\u03b1-deficient CD8\n            <jats:sup>+<\/jats:sup>\n            T cells within the tumor microenvironment, and the cells that do infiltrate exhibit diminished effector functions. Mechanistically, PP2A C\u03b1 deficiency impedes CD28-induced AKT Ser\n            <jats:sup>473<\/jats:sup>\n            phosphorylation, thus impairing CD8\n            <jats:sup>+<\/jats:sup>\n            T cell costimulation signal. Collectively, our findings underscore the critical role of phosphatase PP2A as a propeller for CD28-mediated costimulation signaling in CD8\n            <jats:sup>+<\/jats:sup>\n            T cell effector function by fine-tuning T cell activation.\n          <\/jats:p>","DOI":"10.34133\/research.0545","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T03:33:12Z","timestamp":1732159992000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":3,"title":["Protein Phosphatase 2A Promotes CD8\n            <sup>+<\/sup>\n            T Cell Effector Function through the Augmentation of CD28 Costimulation"],"prefix":"10.34133","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9361-4797","authenticated-orcid":true,"given":"Kaixiang","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Cardiology of The Second Affiliated Hospital, \rZhejiang University School of Medicine, Hangzhou 310009, China."},{"name":"State Key Laboratory of Transvascular Implantation Devices","place":["China"]},{"name":"Heart Regeneration and Repair Key Laboratory of Zhejiang Province","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Rohila","sequence":"additional","affiliation":[{"name":"Institute of Immunology, and Department of Rheumatology in Sir Run Run Shaw Hospital, \rZhejiang University School of Medicine, Hangzhou 310058, China."},{"name":"Sanford Burnham Prebys Medical Discovery Institute","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanling","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Immunology, and Department of Rheumatology in Sir Run Run Shaw Hospital, \rZhejiang University School of Medicine, Hangzhou 310058, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmytro","family":"Shytikov","sequence":"additional","affiliation":[{"name":"Zhejiang University\u2013University of Edinburgh Institute, Zhejiang University School of Medicine, 314400 Haining, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lize","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Immunology, and Department of Rheumatology in Sir Run Run Shaw Hospital, \rZhejiang University School of Medicine, Hangzhou 310058, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Immunology, and Department of Rheumatology in Sir Run Run Shaw Hospital, \rZhejiang University School of Medicine, Hangzhou 310058, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shurong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Second Affiliated Hospital, \rZhejiang University School of Medicine, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Xu","sequence":"additional","affiliation":[{"name":"Cell Signaling and Immunity Section, Laboratory of Immune System Biology (LISB), \rNational Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuexiao","family":"Jin","sequence":"additional","affiliation":[{"name":"Institute of Immunology, and Department of Rheumatology in Sir Run Run Shaw Hospital, \rZhejiang University School of Medicine, Hangzhou 310058, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0171-4115","authenticated-orcid":true,"given":"Linrong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cardiology of The Second Affiliated Hospital, \rZhejiang University School of Medicine, Hangzhou 310009, China."},{"name":"Institute of Immunology, and Department of Rheumatology in Sir Run Run Shaw Hospital, \rZhejiang University School of Medicine, Hangzhou 310058, China."},{"name":"Shanghai Immune Therapy Institute, \rShanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai 200025, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2025,1,2]]},"reference":[{"issue":"1","key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41392-023-01471-y","article-title":"T cells in health and disease","volume":"8","author":"Sun L","year":"2023","unstructured":"Sun L, Su Y, Jiao A, Wang X, Zhang B. 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