{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:45:42Z","timestamp":1789386342828,"version":"build-2803163510"},"reference-count":60,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1996,12,1]]},"abstract":"<jats:p>Previous studies have demonstrated that T cell\u2013reactive antibodies in HIV-1 infection contribute to lymphocyte depletion by cytotoxicity that involves differential membrane targets, such as the 43.5-kD receptor on CEM cells. Here, we show that these antibodies bind Fas as result of a molecular mimicry of the gp120. Both flow cytometry and immunoblotting using the human Fas-transfected mouse WC8 lymphoma revealed positive binding of immunoglobulin G from several patients to a 43.8-kD membrane receptor that also reacts with the CH11 anti-Fas monoclonal antibody. Specificity to Fas was further confirmed to chimeric recombinant human Fas-Fc by ELISA, whereas overlapping peptide mapping of a Fas domain (VEINCTR\u2013N) shared by gp120 V3 loop demonstrated a predominant affinity to the full-length 10-mer peptide. Four anti-Fas affinity preparations greatly increased the subdiploid DNA peak of CEM cells similar to agonist ligands of Fas. In addition, anti-Fas immunoglobulin G strongly inhibited the [3H]thymidine uptake of CEM cells in proliferative assays, inducing a suppression as high as provoked by both CH11 mAb and recombinant human Fas ligand. Since anti-Fas were reactive to gp120, it is conceivable that antibodies binding that domain within the V3 region are effective cross-linkers of Fas and increase apoptosis in peripheral T cells. These results suggest that autologous stimulation of the Fas pathway, rather than of lymphocytotoxic antibodies, may aggravate lymphopenia in a number of HIV-1+ subjects.<\/jats:p>","DOI":"10.1084\/jem.184.6.2287","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"2287-2300","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["Cross-linking of Fas By Antibodies to a Peculiar Domain of gp120 V3 Loop Can Enhance T Cell Apoptosis in HIV-1\u2013infected Patients"],"prefix":"10.1084","volume":"184","author":[{"given":"Franco","family":"Silvestris","sequence":"first","affiliation":[{"name":"From the *Department of Biomedical Sciences and Human Oncology, University of Bari, Section of Internal Medicine, 70124 Bari, Italy; and \u2021Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigekazu","family":"Nagata","sequence":"additional","affiliation":[{"name":"From the *Department of Biomedical Sciences and Human Oncology, University of Bari, Section of Internal Medicine, 70124 Bari, Italy; and \u2021Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Cafforio","sequence":"additional","affiliation":[{"name":"From the *Department of Biomedical Sciences and Human Oncology, University of Bari, Section of Internal Medicine, 70124 Bari, Italy; and \u2021Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Silvestris","sequence":"additional","affiliation":[{"name":"From the *Department of Biomedical Sciences and Human Oncology, University of Bari, Section of Internal Medicine, 70124 Bari, Italy; and \u2021Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Dammacco","sequence":"additional","affiliation":[{"name":"From the *Department of Biomedical Sciences and Human Oncology, University of Bari, Section of Internal Medicine, 70124 Bari, Italy; and \u2021Department of Molecular Biology, Osaka Bioscience Institute, Osaka 565, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1996,12,1]]},"reference":[{"key":"2023072819494000800_B1","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/0042-6822(91)90554-O","article-title":"The cytopathic effect of HIV is associated with apoptosis","volume":"185","author":"Laurent-Crawford","year":"1991","journal-title":"Virology"},{"key":"2023072819494000800_B2","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1172\/JCI115188","article-title":"Apoptosis as a mechanism of cell death in cultured T lymphoblasts acutely infected with HIV-1","volume":"87","author":"Terai","year":"1991","journal-title":"J Clin Invest"},{"key":"2023072819494000800_B3","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1126\/science.1352911","article-title":"Programmed death of T cells in HIV-1 infection","volume":"257","author":"Meyaard","year":"1992","journal-title":"Science (Wash DC)"},{"key":"2023072819494000800_B4","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1006\/smim.1993.1022","article-title":"Direct and indirect mechanism mediating apoptosis during HIV infection: contribution to in vivo CD4 T cell depletion","volume":"5","author":"Gougeon","year":"1993","journal-title":"Semin Immunol"},{"key":"2023072819494000800_B5","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1084\/jem.175.2.331","article-title":"Activation-induced death by apoptosis in CD4+T cells from human immunodeficiency virus\u2013 infected asymptomatic individuals","volume":"175","author":"Groux","year":"1992","journal-title":"J Exp Med"},{"key":"2023072819494000800_B6","doi-asserted-by":"crossref","first-page":"4338","DOI":"10.4049\/jimmunol.150.10.4338","article-title":"Induction of activation-driven death (apoptosis) in activated but not resting peripheral blood T cells","volume":"150","author":"Wesselborg","year":"1993","journal-title":"J Immunol"},{"key":"2023072819494000800_B7","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1172\/JCI117105","article-title":"Programmed death of T cells in human immunodeficiency virus infection. 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