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

dc.creatorTibúrcio, Rafael
dc.creatorNarendran, Gopalan
dc.creatorBarreto-Duarte, Beatriz
dc.creatorQueiroz, Artur T L
dc.creatorAraújo-Pereira, Mariana
dc.creatorAnbalagan, Selvaraj
dc.creatorNayak, Kaustuv
dc.creatorRavichandran, Narayanan
dc.creatorSubramani, Rajasekaran
dc.creatorAntonelli, Lis Ribeiro do Valle
dc.creatorSatagopan, Kumar
dc.creatorAnbalagan, Komathi
dc.creatorPorter, Brian O
dc.creatorSher, Alan
dc.creatorSwaminathan, Soumya
dc.creatorSereti, Irini
dc.creatorAndrade, Bruno B
dc.date2023-03-20T15:39:53Z
dc.date2023-03-20T15:39:53Z
dc.date2022
dc.date.accessioned2023-09-26T20:54:01Z
dc.date.available2023-09-26T20:54:01Z
dc.identifierTIBÚRCIO, Rafael et al. 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. Front Immunol., v. 13, 873985, 2022. doi: 10.3389/fimmu.2022.873985.
dc.identifier1664-3224
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/57459
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8865846
dc.descriptionBackground: 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+ T cell-derived IFN-γ. Nevertheless, the possible participation of CD8+ T cells in TB-IRIS development remains unclear. Methods: We performed a comprehensive assessment of the composition of CD8+ T cell memory subsets and their association with circulating inflammation-related molecules in TB-HIV coinfected patients initiating ART. Results: We found that TB-IRIS individuals display higher frequencies of Antigen-experienced CD8+ 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 naïve CD8+ 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+ 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+ 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+ T cells to the tissues) than Non-IRIS individuals before and after ART. Furthermore, we found that CXCR3+ naïve CD8+ T cells were inversely associated with the risk of TB-IRIS development. On the other hand, we noticed that the frequencies of CXCR3+ effector CD8+ T cells were positively associated with the probability of TB-IRIS development. Conclusion: Our data suggest that TB-IRIS individuals display a distinct profile of memory CD8+ T cell subsets reconstitution after ART initiation. Moreover, our data point to a differential association between the frequencies of CXCR3+ CD8+ T cells and the risk of TB-IRIS development. Collectively, our findings lend insights into the potential role of memory CD8+ T cells in TB-IRIS pathophysiology.
dc.formatapplication/pdf
dc.languageeng
dc.publisherFrontiers Research Foundation
dc.rightsopen access
dc.subjectCD8+ T cells
dc.subjectM. tuberculosis infection
dc.subjectTB-IRIS
dc.subjectimmunologic memory
dc.subjectnaïve lymphocytes
dc.titleFrequency 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
dc.typeArticle


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