{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T06:57:51Z","timestamp":1770101871903,"version":"3.49.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2000,10,1]],"date-time":"2000-10-01T00:00:00Z","timestamp":970358400000},"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":[[2000,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Diabetes in nonobese diabetic (NOD) mice results from the activation of I-Ag7-restricted, islet-reactive T cells. This study delineates several characteristics of NOD CD4 T cell activation, which, independent of I-Ag7, are likely to promote a dysregulated state of peripheral T cell tolerance. NOD CD4 T cell activation was found to be resistant to antigenic stimulation via the TCR complex, using the progression of cell division as a measure. The extent of NOD CD4 T cell division was highly sensitive to changes in Ag ligand density. Moreover, even upon maximal TCR complex-mediated stimulation, NOD CD4 T cell division prematurely terminated. Maximally stimulated NOD CD4 T cells failed to achieve the threshold number of division cycles required for optimal susceptibility to activation-induced death, a critical mechanism for the regulation of peripheral T cell tolerance. Importantly, these aberrant activation characteristics were not T cell-intrinsic but resulted from reliance on B cell costimulatory function in NOD mice. Costimulation delivered by nonautoimmune strain APCs normalized NOD CD4 T cell division and the extent of activation-induced death. Thus, by disrupting the progression of CD4 T cell division, polarization of APC costimulatory function to the B cell compartment could allow the persistence and activation of diabetogenic cells in NOD mice.<\/jats:p>","DOI":"10.4049\/jimmunol.165.8.4685","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:07:54Z","timestamp":1398028074000},"page":"4685-4696","source":"Crossref","is-referenced-by-count":46,"title":["Impaired CD4 T Cell Activation Due to Reliance Upon B Cell-Mediated Costimulation in Nonobese Diabetic (NOD) Mice"],"prefix":"10.1093","volume":"165","author":[{"given":"Hooman","family":"Noorchashm","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren E","family":"Noto","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Negin","family":"Noorchashm","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy J","family":"Reed","sequence":"additional","affiliation":[{"name":"The Wistar Institute , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison L","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard K","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reza","family":"Mozaffari","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony M","family":"Jevnikar","sequence":"additional","affiliation":[{"name":"Division of Nephrology, London Health Sciences Center , London, Ontaro ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clyde F","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Naji","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pennsylvania Medical Center , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,10,15]]},"reference":[{"key":"2026020213110352600_R1","first-page":"601","volume-title":"Nat. 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