{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:56:13Z","timestamp":1789260973907,"version":"build-2803163510"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Clinical evidence for a more active immune response in humans compared with our closest hominid relative, the chimpanzee, includes the progression of HIV infection to AIDS, hepatitis B\u2013 and C\u2013related inflammation, autoimmunity, and unwanted harmful immune responses to viral gene transfer vectors. Humans have a unique mutation of the enzyme CMP-N-acetylneuraminic acid hydroxylase (CMAH), causing loss of expression of the sialic acid Neu5Gc. This mutation, occurring 2 million years ago, likely altered the expression and function of ITIM-bearing inhibitory receptors (Siglecs) that bind sialic acids. Previous work showed that human T cells proliferate faster than chimpanzee T cells upon equivalent stimulation. In this article, we report that Cmah\u2212\/\u2212 mouse T cells proliferate faster and have greater expression of activation markers than wild-type mouse T cells. Metabolically reintroducing Neu5Gc diminishes the proliferation and activation of both human and murine Cmah\u2212\/\u2212 T cells. Importantly, Cmah\u2212\/\u2212 mice mount greater T cell responses to an adenovirus encoding an adeno-associated virus capsid transgene. Upon lymphocytic choriomeningitis virus infection, Cmah\u2212\/\u2212 mice make more lymphocytic choriomeningitis virus\u2013specific T cells than WT mice, and these T cells are more polyfunctional. Therefore, a uniquely human glycosylation mutation, modeled in mice, leads to a more proliferative and active T cell population. These findings in a human-like mouse model have implications for understanding the hyperimmune responses that characterize some human diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1202905","type":"journal-article","created":{"date-parts":[[2013,5,25]],"date-time":"2013-05-25T05:06:01Z","timestamp":1369458361000},"page":"228-237","source":"Crossref","is-referenced-by-count":22,"title":["Enhanced T Cell Function in a Mouse Model of Human Glycosylation"],"prefix":"10.1093","volume":"191","author":[{"given":"George","family":"Buchlis","sequence":"first","affiliation":[{"name":"University of Pennsylvania School of Medicine , Philadelphia, PA 19104"},{"name":"Division of Hematology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Odorizzi","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula C","family":"Soto","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Medicine Department, University of California San Diego , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver M T","family":"Pearce","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Medicine Department, University of California San Diego , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Hui","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha S","family":"Jordan","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajit","family":"Varki","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Medicine Department, University of California San Diego , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E John","family":"Wherry","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A","family":"High","sequence":"additional","affiliation":[{"name":"University of Pennsylvania School of Medicine , Philadelphia, PA 19104"},{"name":"Division of Hematology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104"},{"name":"Howard Hughes Medical Institute , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,7,1]]},"reference":[{"key":"2025032405020025600_r1","volume-title":"Essentials of Glycobiology","author":"Varki","year":"2009","edition":"2nd"},{"key":"2025032405020025600_r2","doi-asserted-by":"crossref","first-page":"11751","DOI":"10.1073\/pnas.95.20.11751","article-title":"A mutation in human CMP-sialic acid hydroxylase occurred after the Homo-Pan divergence","volume":"95","author":"Chou","year":"1998","journal-title":"Proc. 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