{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:12:03Z","timestamp":1792415523584,"version":"4.4.0"},"reference-count":88,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"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":[[2017,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Select CMV epitopes drive life-long CD8+ T cell memory inflation, but the extent of CD4 memory inflation is poorly studied. CD4+ T cells specific for human CMV (HCMV) are elevated in HIV+ HCMV+ subjects. To determine whether HCMV epitope\u2013specific CD4+ T cell memory inflation occurs during HIV infection, we used HLA-DR7 (DRB1*07:01) tetramers loaded with the glycoprotein B DYSNTHSTRYV (DYS) epitope to characterize circulating CD4+ T cells in coinfected HLA-DR7+ long-term nonprogressor HIV subjects with undetectable HCMV plasma viremia. DYS-specific CD4+ T cells were inflated among these HIV+ subjects compared with those from an HIV\u2212 HCMV+ HLA-DR7+ cohort or with HLA-DR7\u2013restricted CD4+ T cells from the HIV-coinfected cohort that were specific for epitopes of HCMV phosphoprotein-65, tetanus toxoid precursor, EBV nuclear Ag 2, or HIV gag protein. Inflated DYS-specific CD4+ T cells consisted of effector memory or effector memory\u2013RA+ subsets with restricted TCR\u03b2 usage and nearly monoclonal CDR3 containing novel conserved amino acids. Expression of this near-monoclonal TCR in a Jurkat cell\u2013transfection system validated fine DYS specificity. Inflated cells were polyfunctional, not senescent, and displayed high ex vivo levels of granzyme B, CX3CR1, CD38, or HLA-DR but less often coexpressed CD38+ and HLA-DR+. The inflation mechanism did not involve apoptosis suppression, increased proliferation, or HIV gag cross-reactivity. Instead, the findings suggest that intermittent or chronic expression of epitopes, such as DYS, drive inflation of activated CD4+ T cells that home to endothelial cells and have the potential to mediate cytotoxicity and vascular disease.<\/jats:p>","DOI":"10.4049\/jimmunol.1700851","type":"journal-article","created":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:20:27Z","timestamp":1506990027000},"page":"3187-3201","source":"Crossref","is-referenced-by-count":56,"title":["Cytomegalovirus (CMV) Epitope\u2013Specific CD4+ T Cells Are Inflated in HIV+ CMV+ Subjects"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0209-8470","authenticated-orcid":false,"given":"Chike O","family":"Abana","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine , Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1318-8279","authenticated-orcid":false,"given":"Mark A","family":"Pilkinton","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6873-0198","authenticated-orcid":false,"given":"Silvana","family":"Gaudieri","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN 37232"},{"name":"School of Human Sciences, University of Western Australia , Perth, Western Australia 6009,","place":["Australia"]},{"name":"Institute for Immunology and Infectious Diseases, Murdoch University , Murdoch, Western Australia 6150,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abha","family":"Chopra","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Infectious Diseases, Murdoch University , Murdoch, Western Australia 6150,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3859-2067","authenticated-orcid":false,"given":"Wyatt J","family":"McDonnell","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine , Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celestine","family":"Wanjalla","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN 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Transplantation, Division of Hematology\/Oncology, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian G","family":"Engelhardt","sequence":"additional","affiliation":[{"name":"Stem Cell Transplantation, Division of Hematology\/Oncology, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madan H","family":"Jagasia","sequence":"additional","affiliation":[{"name":"Stem Cell Transplantation, Division of Hematology\/Oncology, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4307-9161","authenticated-orcid":false,"given":"Paul","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research, University of Oxford , Oxford OX1 3SY,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine , Nashville, TN 37232"},{"name":"Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN 37232"},{"name":"Institute for Immunology and Infectious Diseases, Murdoch University , Murdoch, Western Australia 6150,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1255-9023","authenticated-orcid":false,"given":"David M","family":"Koelle","sequence":"additional","affiliation":[{"name":"Department of Medicine, Laboratory Medicine, and Global Health, University of Washington , Seattle, WA 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