{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:50:27Z","timestamp":1791341427893,"version":"4.3.1"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2001,8,1]],"date-time":"2001-08-01T00:00:00Z","timestamp":996624000000},"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":[[2001,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A costimulatory member of the TNFR family, 4-1BB, is expressed on activated T cells. Although some reports have suggested that 4-1BB is primarily involved in CD8 T cell activation, in this report we demonstrate that both CD4 and CD8 T cells respond to 4-1BB ligand (4-1BBL) with similar efficacy. CD4 and CD8 TCR transgenic T cells up-regulate 4-1BB, OX40, and CD27 and respond to 4-1BBL-mediated costimulation during a primary response to peptide Ag. 4-1BBL enhanced proliferation, cytokine production, and CTL effector function of TCR transgenic T cells. To compare CD4 vs CD8 responses to 4-1BBL under similar conditions of antigenic stimulation, we performed MLRs with purified CD4 or CD8 responders from CD28+\/+ and CD28\u2212\/\u2212 mice. We found that CD8 T cells produced IL-2 and IFN-\u03b3 in a 4-1BBL-dependent manner, whereas under the same conditions the CD4 T cells produced IL-2 and IL-4. 4-1BBL promoted survival of CD4 and CD8 T cells, particularly at late stages of the MLR. CD4 and CD8 T cells both responded to anti-CD3 plus s4-1BBL with a similar cytokine profile as observed in the MLR. CD4 and CD8 T cells exhibited enhanced proliferation and earlier cell division when stimulated with anti-CD3 plus anti-CD28 compared with anti-CD3 plus 4-1BBL, and both subsets responded comparably to anti-CD3 plus 4-1BBL. These data support the idea that CD28 plays a primary role in initial T cell expansion, whereas 4-1BB\/4-1BBL sustains both CD4 and CD8 T cell responses, as well as enhances cell division and T cell effector function.<\/jats:p>","DOI":"10.4049\/jimmunol.167.3.1313","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T23:31:49Z","timestamp":1398123109000},"page":"1313-1324","source":"Crossref","is-referenced-by-count":264,"title":["4-1BB Ligand Induces Cell Division, Sustains Survival, and Enhances Effector Function of CD4 and CD8 T Cells with Similar Efficacy"],"prefix":"10.1093","volume":"167","author":[{"given":"Jennifer L","family":"Cannons","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birinder","family":"Ghumman","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A","family":"DeBenedette","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Yagita","sequence":"additional","affiliation":[{"name":"Department of Immunology, Juntendo University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ko","family":"Okumura","sequence":"additional","affiliation":[{"name":"Department of Immunology, Juntendo University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania H","family":"Watts","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2001,8,1]]},"reference":[{"key":"2026020209120094400_R1","first-page":"233","volume-title":"Annu. 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