{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T22:21:43Z","timestamp":1770416503314,"version":"3.49.0"},"reference-count":109,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>T follicular helper (T<jats:sub>FH<\/jats:sub>) cells are pivotal in lymph node (LN) germinal center (GC) B cell affinity maturation. Circulating CXCR5<jats:sup>+<\/jats:sup> CD4<jats:sup>+<\/jats:sup> T (cT<jats:sub>FH<\/jats:sub>) cells have supported memory B cell activation and broadly neutralizing antibodies in HIV controllers. We investigated the contribution of LN SIV-specific T<jats:sub>FH<\/jats:sub> and cT<jats:sub>FH<\/jats:sub> cells to Env-specific humoral immunity in female rhesus macaques following a mucosal Ad5hr-SIV recombinant priming and SIV gp120 intramuscular boosting vaccine regimen and following SIV vaginal challenge. T<jats:sub>FH<\/jats:sub> and B cells were characterized by flow cytometry. B cell help was evaluated in T<jats:sub>FH<\/jats:sub>-B cell co-cultures and by real-time PCR. Vaccination induced Env-specific T<jats:sub>FH<\/jats:sub> and Env-specific memory (ESM) B cells in LNs. LN Env-specific T<jats:sub>FH<\/jats:sub> cells post-priming and GC ESM B cells post-boosting correlated with rectal Env-specific IgA titers, and GC B cells at the same timepoints correlated with vaginal Env-specific IgG titers. Vaccination expanded cT<jats:sub>FH<\/jats:sub> cell responses, including CD25<jats:sup>+<\/jats:sup> Env-specific cT<jats:sub>FH<\/jats:sub> cells that correlated negatively with vaginal Env-specific IgG titers but positively with rectal Env-specific IgA titers. Although cT<jats:sub>FH<\/jats:sub> cells post-2<jats:sup>nd<\/jats:sup> boost positively correlated with viral-loads following SIV challenge, cT<jats:sub>FH<\/jats:sub> cells of SIV-infected and protected macaques supported maturation of circulating B cells into plasma cells and IgA release in co-culture. Additionally, cT<jats:sub>FH<\/jats:sub> cells of na\u00efve macaques promoted upregulation of genes associated with B cell proliferation, BCR engagement, plasma cell maturation, and antibody production, highlighting the role of cT<jats:sub>FH<\/jats:sub> cells in blood B cell maturation. Vaccine-induced LN T<jats:sub>FH<\/jats:sub> and GC B cells supported anti-viral mucosal immunity while cT<jats:sub>FH<\/jats:sub> cells provided B cell help in the periphery during immunization and after SIV challenge. Induction of T<jats:sub>FH<\/jats:sub> responses in blood and secondary lymphoid organs is likely desirable for protective efficacy of HIV vaccines.<\/jats:p>","DOI":"10.3389\/fimmu.2020.608003","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T05:35:16Z","timestamp":1611812116000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["TFH Cells Induced by Vaccination and Following SIV Challenge Support Env-Specific Humoral Immunity in the Rectal-Genital Tract and Circulation of Female Rhesus Macaques"],"prefix":"10.3389","volume":"11","author":[{"given":"Sabrina","family":"Helmold Hait","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher James","family":"Hogge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad 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