{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:58:32Z","timestamp":1784959112310,"version":"3.55.0"},"reference-count":83,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health","award":["NIH, ZIA SC009172"],"award-info":[{"award-number":["NIH, ZIA SC009172"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thrombospondin-1 potently inhibits T cell activation by engaging its cell surface receptor CD47. This inhibitory signal requires glycosaminoglycan modification of CD47. CD47 also regulates the composition of RNAs in extracellular vesicles released by T cells and their functional activities. Because CD47 is also present in extracellular vesicles, we examined the effect of T cell activation on CD47 glycoforms in T cells and extracellular vesicles released by these cells. Activation increased both heparan and chondroitin sulfate biosynthesis by globally inducing mRNA levels of the respective glycosaminoglycan synthases and sulfotransferases. T cell activation in the presence of thrombospondin-1 inhibited induction of these biosynthetic enzymes, but not in cells lacking CD47. Therefore, CD47 signaling controls its own post-translational modification by glycosaminoglycans that are required for thrombospondin-1 signaling. Activation of Jurkat T lymphoblasts and primary CD4 and CD8 T cells increased the release of proteoglycan isoforms of CD47 and amyloid precursor-like protein-2 associated with extracellular vesicles and smaller macromolecular complexes. However, cell surface levels of CD47 were minimally changed during activation. BJAB and RAJI B cell lines also produced CD47+ extracellular vesicles and showed increased release of highly glycosylated CD47 following B cell receptor engagement. Therefore, T and B lymphocyte activation results in a selective increase in the synthesis and release of extracellular vesicles containing proteoglycan isoforms of CD47.<\/jats:p>","DOI":"10.3390\/ijms26178377","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T08:01:01Z","timestamp":1756454461000},"page":"8377","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["T Cell Activation Induces Synthesis of CD47 Proteoglycan Isoforms and Their Release in Extracellular Vesicles"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0513-6225","authenticated-orcid":false,"given":"Sukhbir","family":"Kaur","sequence":"first","affiliation":[{"name":"Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20982, USA"},{"name":"HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20982, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana A.","family":"Kuznetsova","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20982, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Sipes","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20982, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satya P.","family":"Singh","sequence":"additional","affiliation":[{"name":"Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8956-2979","authenticated-orcid":false,"given":"Rafael","family":"Villasmil","sequence":"additional","affiliation":[{"name":"Flow Cytometry Core Facility, National Eye Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2481-2981","authenticated-orcid":false,"given":"David D.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20982, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0304-4165(00)00079-9","article-title":"Distribution of sulfated glycosaminoglycans in the animal kingdom: Widespread occurrence of heparin-like compounds in invertebrates","volume":"1475","author":"Medeiros","year":"2000","journal-title":"Biochim. 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