{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:02:49Z","timestamp":1792789369375,"version":"4.5.0"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5121","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1993,7,30]]},"abstract":"<jats:p>\n                    T cell receptor stimulation without costimulation is insufficient for the induction of an optimal immune response. It is thought that engagement of the CD28 molecule with its ligand B7 provides an essential costimulatory signal without which full activation of T cells cannot occur. A mouse strain with a defective CD28 gene was established. Development of T and B cells in the CD28-deficient mice appeared normal. However, T lymphocytes derived from CD28\n                    <jats:sup>-\/-<\/jats:sup>\n                    mutant mice had impaired responses to lectins. Lectin stimulation did not trigger interleukin-2 (IL-2) production, IL-2 receptor \u03b1 expression was significantly decreased, and exogenous IL-2 only partially rescued the CD28 defect. Basal immunoglobulin (Ig) concentrations in CD28-deficient mice were about one-fifth of those found in wild-type controls, with low titers of IgG1 and IgG2b but an increase in IgG2a. In addition, activity of T helper cells in CD28\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice was reduced and immunoglobulin class switching was diminished after infection with vesicular stomatitis virus. However, cytotoxic T cells could still be induced and the mice showed delayed-type hypersensitivity after infection with lymphocytic choriomeningitis virus. Thus, CD28 is not required for all T cell responses in vivo, suggesting that alternative costimulatory pathways may exist.\n                  <\/jats:p>","DOI":"10.1126\/science.7688139","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T19:05:09Z","timestamp":1160075109000},"page":"609-612","source":"Crossref","is-referenced-by-count":873,"title":["Differential T Cell Costimulatory Requirements in CD28-Deficient Mice"],"prefix":"10.1126","volume":"261","author":[{"given":"Arda","family":"Shahinian","sequence":"first","affiliation":[{"name":"Amgen Institute, Department of Medical Biophysics and Immunology, Ontario Cancer Institute, University of Toronto, Toronto M4X 1 K9, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Amgen Institute, Department of Medical Biophysics and Immunology, Ontario Cancer Institute, University of Toronto, Toronto M4X 1 K9, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin P.","family":"Lee","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"K\u00fcndig","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics and Immunology, Ontario Cancer Institute, Toronto M4X 1 K9, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Kishihara","sequence":"additional","affiliation":[{"name":"Amgen Institute, Department of Medical Biophysics and Immunology, Ontario Cancer Institute, University of Toronto, Toronto M4X 1 K9, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wakeham","sequence":"additional","affiliation":[{"name":"Amgen Institute, Department of Medical Biophysics and Immunology, Ontario Cancer Institute, University of Toronto, Toronto M4X 1 K9, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Kawai","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics and Immunology, Ontario Cancer Institute, Toronto M4X 1 K9, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela S.","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics and Immunology, Ontario Cancer Institute, Toronto M4X 1 K9, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig B.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tak W.","family":"Mak","sequence":"additional","affiliation":[{"name":"Amgen Institute, Department of Medical Biophysics and Immunology, Ontario Cancer Institute, University of Toronto, Toronto M4X 1 K9, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"crossref","first-page":"3429","DOI":"10.4049\/jimmunol.149.11.3429","volume":"149","year":"1992","unstructured":"ABE, R, CHARACTERIZATION OF THE MLS(F) SYSTEM .1. 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