{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:19:47Z","timestamp":1790716787327,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Antigen-specific CD4\n            <jats:sup>+<\/jats:sup>\n            T helper cell responses have long been recognized to be a critical component of effective vaccine immunity. CD4\n            <jats:sup>+<\/jats:sup>\n            T cells are necessary to generate and maintain humoral immune responses by providing help to antigen-specific B cells for the production of antibodies. In HIV infection, CD4\n            <jats:sup>+<\/jats:sup>\n            T cells are thought to be necessary for the induction of Env-specific broadly neutralizing antibodies. However, few studies have investigated the role of HIV-specific CD4\n            <jats:sup>+<\/jats:sup>\n            T cells in association with HIV neutralizing antibody activity in vaccination or natural infection settings. Here, we conducted a comprehensive analysis of HIV-specific CD4\n            <jats:sup>+<\/jats:sup>\n            T cell responses in a cohort of 34 untreated HIV-infected controllers matched for viral load, with and without neutralizing antibody breadth to a panel of viral strains. Our results show that the breadth and magnitude of Gag-specific CD4\n            <jats:sup>+<\/jats:sup>\n            T cell responses were significantly higher in individuals with neutralizing antibodies than in those without neutralizing antibodies. The breadth of Gag-specific CD4\n            <jats:sup>+<\/jats:sup>\n            T cell responses was positively correlated with the breadth of neutralizing antibody activity. Furthermore, the breadth and magnitude of gp41-specific, but not gp120-specific, CD4\n            <jats:sup>+<\/jats:sup>\n            T cell responses were significantly elevated in individuals with neutralizing antibodies. Together, these data suggest that robust Gag-specific CD4\n            <jats:sup>+<\/jats:sup>\n            T cells and, to a lesser extent, gp41-specific CD4\n            <jats:sup>+<\/jats:sup>\n            T cells may provide important intermolecular help to Env-specific B cells that promote the generation or maintenance of Env-specific neutralizing antibodies.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            One of the earliest discoveries related to CD4\n            <jats:sup>+<\/jats:sup>\n            T cell function was their provision of help to B cells in the development of antibody responses. Yet little is known about the role of CD4\n            <jats:sup>+<\/jats:sup>\n            T helper responses in the setting of HIV infection, and no studies to date have evaluated the impact of HIV-specific CD4\n            <jats:sup>+<\/jats:sup>\n            T cells on the generation of antibodies that can neutralize multiple different strains of HIV. Here, we addressed this question by analyzing HIV-specific CD4\n            <jats:sup>+<\/jats:sup>\n            T cell responses in untreated HIV-infected persons with and without neutralizing antibodies. Our results indicate that HIV-infected persons with neutralizing antibodies have significantly more robust CD4\n            <jats:sup>+<\/jats:sup>\n            T cell responses targeting Gag and gp41 proteins than individuals who lack neutralizing antibodies. These associations suggest that Gag- and gp41-specific CD4\n            <jats:sup>+<\/jats:sup>\n            T cell responses may provide robust help to B cells for the generation or maintenance of neutralizing antibodies in natural HIV-infection.\n          <\/jats:p>","DOI":"10.1128\/jvi.02278-15","type":"journal-article","created":{"date-parts":[[2015,12,11]],"date-time":"2015-12-11T12:54:04Z","timestamp":1449838444000},"page":"2208-2220","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["HIV-1 Antibody Neutralization Breadth Is Associated with Enhanced HIV-Specific CD4\n            <sup>+<\/sup>\n            T Cell Responses"],"prefix":"10.1128","volume":"90","author":[{"given":"Srinika","family":"Ranasinghe","sequence":"first","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital and Harvard Medical School, Cambridge, Massachusetts, USA"},{"name":"Center for HIV\/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien Z.","family":"Soghoian","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital and Harvard Medical School, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madelene","family":"Lindqvist","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital and Harvard Medical School, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musie","family":"Ghebremichael","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital and Harvard Medical School, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faith","family":"Donaghey","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital and Harvard Medical School, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Carrington","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital and Harvard Medical School, Cambridge, Massachusetts, USA"},{"name":"Cancer and Inflammation Program, HLA Immunogenetics Section, Leidos Biomedical Research, Inc., National Cancer Institute, Frederick, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Seaman","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital and Harvard Medical School, Cambridge, Massachusetts, USA"},{"name":"Center for HIV\/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, USA"},{"name":"Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D.","family":"Walker","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital and Harvard Medical School, Cambridge, Massachusetts, USA"},{"name":"Center for HIV\/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippos","family":"Porichis","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital and Harvard Medical School, Cambridge, Massachusetts, USA"},{"name":"Center for HIV\/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, 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