{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:56:44Z","timestamp":1753891004467,"version":"3.41.2"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"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:sec><jats:title>Background<\/jats:title><jats:p>Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a clinical aggravation of TB symptoms observed among a fraction of HIV coinfected patients shortly after the start of antiretroviral therapy (ART). Of note, TB-IRIS is characterized by exacerbated inflammation and tissue damage that occurs in response to the elevated production of CD4<jats:sup>+<\/jats:sup> T cell-derived IFN-\u03b3. Nevertheless, the possible participation of CD8<jats:sup>+<\/jats:sup> T cells in TB-IRIS development remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a comprehensive assessment of the composition of CD8<jats:sup>+<\/jats:sup> T cell memory subsets and their association with circulating inflammation-related molecules in TB-HIV coinfected patients initiating ART.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that TB-IRIS individuals display higher frequencies of Antigen-experienced CD8<jats:sup>+<\/jats:sup> T cells during the onset of IRIS and that the levels of these cells positively correlate with baseline mycobacterial smear grade. TB-IRIS individuals exhibited higher frequencies of effector memory and lower percentages of na\u00efve CD8<jats:sup>+<\/jats:sup> T cells than their Non-IRIS counterparts. In both TB-IRIS and Non-IRIS patients, ART commencement was associated with fewer significant correlations among memory CD8<jats:sup>+<\/jats:sup> T cells and cells from other immune compartments. Networks analysis revealed distinct patterns of correlation between each memory subset with inflammatory cytokines suggesting different dynamics of CD8<jats:sup>+<\/jats:sup> T cell memory subsets reconstitution. TB-IRIS patients displayed lower levels of memory cells positive for CXCR3 (a chemokine receptor that plays a role in trafficking activated CD8<jats:sup>+<\/jats:sup> T cells to the tissues) than Non-IRIS individuals before and after ART. Furthermore, we found that CXCR3<jats:sup>+<\/jats:sup> na\u00efve CD8<jats:sup>+<\/jats:sup> T cells were inversely associated with the risk of TB-IRIS development. On the other hand, we noticed that the frequencies of CXCR3<jats:sup>+<\/jats:sup> effector CD8<jats:sup>+<\/jats:sup> T cells were positively associated with the probability of TB-IRIS development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that TB-IRIS individuals display a distinct profile of memory CD8<jats:sup>+<\/jats:sup> T cell subsets reconstitution after ART initiation. Moreover, our data point to a differential association between the frequencies of CXCR3<jats:sup>+<\/jats:sup> CD8<jats:sup>+<\/jats:sup> T cells and the risk of TB-IRIS development. Collectively, our findings lend insights into the potential role of memory CD8<jats:sup>+<\/jats:sup> T cells in TB-IRIS pathophysiology.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.873985","type":"journal-article","created":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T09:59:22Z","timestamp":1648807162000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Frequency of CXCR3+ CD8+ T-Lymphocyte Subsets in Peripheral Blood Is Associated With the Risk of Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome Development in Advanced HIV Disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Rafael","family":"Tib\u00farcio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gopalan","family":"Narendran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Barreto-Duarte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Artur T. 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