{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T20:09:10Z","timestamp":1771618150058,"version":"3.50.1"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"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>Follicular-helper T cells (T<jats:sub>FH<\/jats:sub>) are an essential arm of the adaptive immune system. Although T<jats:sub>FH<\/jats:sub> were first discovered through their ability to contribute to antibody affinity maturation through co-stimulatory interactions with B cells, new light has been shed on their ability to remain a complex and functionally plastic cell type. Due to a lack sample availability, however, many studies have been limited to characterizing T<jats:sub>FH<\/jats:sub> in mice or non-canonical tissue types, such as peripheral blood. Such constraints have resulted in a limited, and sometimes contradictory, understanding of this fundamental cell type. One subset of T<jats:sub>FH<\/jats:sub> receiving attention in chronic infection are CXCR3-expressing T<jats:sub>FH<\/jats:sub> cells (CXCR3<jats:sup>+<\/jats:sup>T<jats:sub>FH<\/jats:sub>) due to their abnormal accumulation in secondary lymphoid tissues. Their function and clonal relationship with other T<jats:sub>FH<\/jats:sub> subsets in lymphoid tissues during infection, however, remains largely unclear. We thus systematically investigated this and other subsets of T<jats:sub>FH<\/jats:sub> within untreated HIV-infected human lymph nodes using Mass CyTOF and a combination of RNA and TCR repertoire sequencing. We show an inflation of the CXCR3<jats:sup>+<\/jats:sup>T<jats:sub>FH<\/jats:sub> compartment during HIV infection that correlates with a lower HIV burden. Deeper analysis into this population revealed a functional shift of CXCR3<jats:sup>+<\/jats:sup>T<jats:sub>FH<\/jats:sub> away from germinal center T<jats:sub>FH<\/jats:sub> (GC-T<jats:sub>FH<\/jats:sub>), including the altered expression of several important transcription factors and cytokines. CXCR3<jats:sup>+<\/jats:sup>T<jats:sub>FH<\/jats:sub> also upregulated cell migration transcriptional programs and were clonally related to peripheral T<jats:sub>FH<\/jats:sub> populations. In combination, these data suggest that CXCR3<jats:sup>+<\/jats:sup>T<jats:sub>FH<\/jats:sub> have a greater tendency to enter circulation than their CXCR3<jats:sup>-<\/jats:sup> counterparts, potentially functioning through distinct modalities that may lead to enhanced defense.<\/jats:p>","DOI":"10.3389\/fimmu.2022.859070","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T06:57:26Z","timestamp":1651820246000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Transcriptome and TCR Repertoire Measurements of CXCR3+ T Follicular Helper Cells Within HIV-Infected Human Lymph Nodes"],"prefix":"10.3389","volume":"13","author":[{"given":"Chenfeng","family":"He","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael 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