{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T14:18:14Z","timestamp":1768313894209,"version":"3.49.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"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":[[2012,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>\u03b3\u03b4 T cells play key nonredundant roles in immunity to infections and tumors. Thus, it is critical to understand the molecular mechanisms responsible for \u03b3\u03b4 T cell activation and expansion in vivo. In striking contrast to their \u03b1\u03b2 counterparts, the costimulation requirements of \u03b3\u03b4 T cells remain poorly understood. Having previously described a role for the TNFR superfamily member CD27, we since screened for other nonredundant costimulatory receptors in \u03b3\u03b4 T cell activation. We report in this article that the Ig superfamily receptor CD28 (but not its related protein ICOS) is expressed on freshly isolated lymphoid \u03b3\u03b4 T cells and synergizes with the TCR to induce autocrine IL-2 production that promotes \u03b3\u03b4 cell survival and proliferation in both mice and humans. Specific gain-of-function and loss-of-function experiments demonstrated a nonredundant function for CD28 interactions with its B7 ligands, B7.1 (CD80) and B7.2 (CD86), both in vitro and in vivo. Thus, \u03b3\u03b4 cell proliferation was significantly enhanced by CD28 receptor agonists but abrogated by B7 Ab-mediated blockade. Furthermore, \u03b3\u03b4 cell expansion following Plasmodium infection was severely impaired in mice genetically deficient for CD28. This resulted in the failure to mount both IFN-\u03b3\u2013mediated and IL-17\u2013mediated \u03b3\u03b4 cell responses, which contrasted with the selective effect of CD27 on IFN-\u03b3\u2013producing \u03b3\u03b4 cells. Our data collectively show that CD28 signals are required for IL-2\u2013mediated survival and proliferation of both CD27+ and CD27\u2212 \u03b3\u03b4 T cell subsets, thus providing new mechanistic insight for their modulation in disease models.<\/jats:p>","DOI":"10.4049\/jimmunol.1200268","type":"journal-article","created":{"date-parts":[[2012,6,26]],"date-time":"2012-06-26T18:29:32Z","timestamp":1340735372000},"page":"1202-1208","source":"Crossref","is-referenced-by-count":77,"title":["B7\u2013CD28 Costimulatory Signals Control the Survival and Proliferation of Murine and Human \u03b3\u03b4 T Cells via IL-2 Production"],"prefix":"10.1093","volume":"189","author":[{"given":"Julie C","family":"Ribot","sequence":"first","affiliation":[{"name":"Unidade de Imunologia Molecular, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , 1649-028 Lisboa,","place":["Portugal"]}]},{"given":"Ana","family":"deBarros","sequence":"additional","affiliation":[{"name":"Unidade de Imunologia Molecular, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , 1649-028 Lisboa,","place":["Portugal"]}]},{"given":"Liliana","family":"Mancio-Silva","sequence":"additional","affiliation":[{"name":"Unidade de Imunologia Molecular, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , 1649-028 Lisboa,","place":["Portugal"]},{"name":"Unidade de Mal\u00e1ria, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , 1649-028 Lisboa,","place":["Portugal"]}]},{"given":"Ana","family":"Pamplona","sequence":"additional","affiliation":[{"name":"Unidade de Imunologia Molecular, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , 1649-028 Lisboa,","place":["Portugal"]}]},{"given":"Bruno","family":"Silva-Santos","sequence":"additional","affiliation":[{"name":"Unidade de Imunologia Molecular, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , 1649-028 Lisboa,","place":["Portugal"]},{"name":"Instituto Gulbenkian de Ci\u00eancia , 2781-901 Oeiras,","place":["Portugal"]}]}],"member":"286","published-online":{"date-parts":[[2012,8,1]]},"reference":[{"key":"2025032409213998800_r1","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1146\/annurev.immunol.18.1.975","article-title":"[gamma][delta] cells: a right time and a right place for a conserved third way of protection","volume":"18","author":"Hayday","year":"2000","journal-title":"Annu. 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