{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:33:08Z","timestamp":1791282788616,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"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":[[2016,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>HIV-1 replication is concentrated within CD4+ T cells in B cell follicles of secondary lymphoid tissues during asymptomatic disease. Limited data suggest that a subset of T follicular helper cells (TFH) within germinal centers (GC) is highly permissive to HIV-1. Whether GC TFH are the major HIV-1 virus\u2013producing cells in vivo has not been established. In this study, we investigated TFH permissivity to HIV-1 ex vivo by spinoculating and culturing tonsil cells with HIV-1 GFP reporter viruses. Using flow cytometry, higher percentages of GC TFH (CXCR5highPD-1high) and CXCR5+programmed cell death-1 (PD-1)low cells were GFP+ than non-GC TFH (CXCR5+PD-1intermediate) or extrafollicular (EF) (CXCR5\u2212) cells. When sorted prior to spinoculation, however, GC TFH were substantially more permissive than CXCR5+PD-1low or EF cells, suggesting that many GC TFH transition to a CXCR5+PD-1low phenotype during productive infection. In situ hybridization on inguinal lymph node sections from untreated HIV-1\u2013infected individuals without AIDS revealed higher frequencies of HIV-1 RNA+ cells in GC than non-GC regions of follicle or EF regions. Superinfection of HIV-1\u2013infected individuals\u2019 lymph node cells with GFP reporter virus confirmed the permissivity of follicular cells ex vivo. Lymph node immunostaining revealed 96% of CXCR5+CD4+ cells were located in follicles. Within sorted lymph node cells from four HIV-infected individuals, CXCR5+ subsets harbored 11\u201366-fold more HIV-1 RNA than CXCR5\u2212 subsets, as determined by RT PCR. Thus, GC TFH are highly permissive to HIV-1, but downregulate PD-1 and, to a lesser extent, CXCR5 during HIV-1 replication. These data further implicate GC TFH as the major HIV-1\u2013producing cells in chronic asymptomatic HIV-1 infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1502174","type":"journal-article","created":{"date-parts":[[2016,2,13]],"date-time":"2016-02-13T07:18:41Z","timestamp":1455347921000},"page":"2711-2722","source":"Crossref","is-referenced-by-count":96,"title":["Germinal Center T Follicular Helper Cells Are Highly Permissive to HIV-1 and Alter Their Phenotype during Virus Replication"],"prefix":"10.1093","volume":"196","author":[{"given":"Stephanie L","family":"Kohler","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael N","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy M","family":"Folkvord","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Arends","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon M","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brodie","family":"Miles","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2889-8476","authenticated-orcid":false,"given":"Amie L","family":"Meditz","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"McCarter","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Colorado Anschutz Medical Campus , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9389-5509","authenticated-orcid":false,"given":"David N","family":"Levy","sequence":"additional","affiliation":[{"name":"College of Dentistry, New York University , New York, NY 10010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Connick","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,3,15]]},"reference":[{"key":"2025030702150764200_r1","doi-asserted-by":"crossref","first-page":"5613","DOI":"10.4049\/jimmunol.1401161","article-title":"Compartmentalization of simian immunodeficiency virus replication within secondary lymphoid tissues of rhesus macaques is linked to disease stage and inversely related to localization of virus-specific CTL","volume":"193","author":"Connick","year":"2014","journal-title":"J. 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