{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:16:37Z","timestamp":1791353797042,"version":"4.3.1"},"reference-count":29,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,4,5]]},"abstract":"<jats:p>CD40 ligand (CD40L), a tumor necrosis factor (TNF) family member, plays a critical role in antigen-specific T cell responses in vivo. CD40L expressed on activated CD4+ T cells stimulates antigen-presenting cells such as dendritic cells, resulting in the upregulation of costimulatory molecules and the production of various inflammatory cytokines required for CD4+ T cell priming in vivo. However, CD40L- or CD40-deficient mice challenged with viruses mount protective CD4+ T cell responses that produce normal levels of interferon \u03b3, suggesting a CD40L\/CD40-independent mechanism of CD4+ T cell priming that to date has not been elucidated. Here we show that CD4+ T cell responses to viral infection were greatly diminished in CD40-deficient mice by administration of a soluble form of TNF-related activation-induced cytokine receptor (TRANCE-R) to inhibit the function of another TNF family member, TRANCE. Thus, the TRANCE\/TRANCE-R interaction provides costimulation required for efficient CD4+ T cell priming during viral infection in the absence of CD40L\/CD40. These results also indicate that not even the potent inflammatory microenvironment induced by viral infections is sufficient to elicit efficient CD4+ T cell priming without proper costimulation provided by the TNF family (CD40L or TRANCE). Moreover, the data suggest that TRANCE\/TRANCE-R may be a novel and important target for immune intervention.<\/jats:p>","DOI":"10.1084\/jem.189.7.1025","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"1025-1031","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":186,"title":["TRANCE, a Tumor Necrosis Factor Family Member Critical for CD40 Ligand\u2013independent T Helper Cell Activation"],"prefix":"10.1084","volume":"189","author":[{"given":"Martin F.","family":"Bachmann","sequence":"first","affiliation":[{"name":"From the *Basel Institute for Immunology, CH 4005 Basel, Switzerland; the \u2021Institute for Experimental Immunology, 8019 Z\u00fcrich, Switzerland; and the \u00a7Laboratory of Cellular Physiology and Immunology, the \u2016Laboratory of Immunology, and the \u00b6Howard Hughes Medical Institute, The Rockefeller University, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R.","family":"Wong","sequence":"additional","affiliation":[{"name":"From the *Basel Institute for Immunology, CH 4005 Basel, Switzerland; the \u2021Institute for Experimental Immunology, 8019 Z\u00fcrich, Switzerland; and the \u00a7Laboratory of Cellular Physiology and Immunology, the \u2016Laboratory of Immunology, and the \u00b6Howard Hughes Medical Institute, The Rockefeller University, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9gis","family":"Josien","sequence":"additional","affiliation":[{"name":"From the *Basel Institute for Immunology, CH 4005 Basel, Switzerland; the \u2021Institute for Experimental Immunology, 8019 Z\u00fcrich, Switzerland; and the \u00a7Laboratory of Cellular Physiology and Immunology, the \u2016Laboratory of Immunology, and the \u00b6Howard Hughes Medical Institute, The Rockefeller University, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph M.","family":"Steinman","sequence":"additional","affiliation":[{"name":"From the *Basel Institute for Immunology, CH 4005 Basel, Switzerland; the \u2021Institute for Experimental Immunology, 8019 Z\u00fcrich, Switzerland; and the \u00a7Laboratory of Cellular Physiology and Immunology, the \u2016Laboratory of Immunology, and the \u00b6Howard Hughes Medical Institute, The Rockefeller University, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Oxenius","sequence":"additional","affiliation":[{"name":"From the *Basel Institute for Immunology, CH 4005 Basel, Switzerland; the \u2021Institute for Experimental Immunology, 8019 Z\u00fcrich, Switzerland; and the \u00a7Laboratory of Cellular Physiology and Immunology, the \u2016Laboratory of Immunology, and the \u00b6Howard Hughes Medical Institute, The Rockefeller University, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongwon","family":"Choi","sequence":"additional","affiliation":[{"name":"From the *Basel Institute for Immunology, CH 4005 Basel, Switzerland; the \u2021Institute for Experimental Immunology, 8019 Z\u00fcrich, Switzerland; and the \u00a7Laboratory of Cellular Physiology and Immunology, the \u2016Laboratory of Immunology, and the \u00b6Howard Hughes Medical Institute, The Rockefeller University, New York 10021"},{"name":"From the *Basel Institute for Immunology, CH 4005 Basel, Switzerland; the \u2021Institute for Experimental Immunology, 8019 Z\u00fcrich, Switzerland; and the \u00a7Laboratory of Cellular Physiology and Immunology, the \u2016Laboratory of Immunology, and the \u00b6Howard Hughes Medical Institute, The Rockefeller University, New York 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