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
BackgroundTuberculosis-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...
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Frontiers Media S.A.
2022-04-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.873985/full |
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| author | Rafael Tibúrcio Rafael Tibúrcio Rafael Tibúrcio Gopalan Narendran Beatriz Barreto-Duarte Beatriz Barreto-Duarte Beatriz Barreto-Duarte Beatriz Barreto-Duarte Artur T. L. Queiroz Artur T. L. Queiroz Mariana Araújo-Pereira Mariana Araújo-Pereira Mariana Araújo-Pereira Selvaraj Anbalagan Kaustuv Nayak Kaustuv Nayak Narayanan Ravichandran Rajasekaran Subramani Lis R. V. Antonelli Kumar Satagopan Komathi Anbalagan Brian O. Porter Alan Sher Soumya Swaminathan Irini Sereti Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade |
| author_facet | Rafael Tibúrcio Rafael Tibúrcio Rafael Tibúrcio Gopalan Narendran Beatriz Barreto-Duarte Beatriz Barreto-Duarte Beatriz Barreto-Duarte Beatriz Barreto-Duarte Artur T. L. Queiroz Artur T. L. Queiroz Mariana Araújo-Pereira Mariana Araújo-Pereira Mariana Araújo-Pereira Selvaraj Anbalagan Kaustuv Nayak Kaustuv Nayak Narayanan Ravichandran Rajasekaran Subramani Lis R. V. Antonelli Kumar Satagopan Komathi Anbalagan Brian O. Porter Alan Sher Soumya Swaminathan Irini Sereti Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade |
| author_sort | Rafael Tibúrcio |
| collection | DOAJ |
| description | BackgroundTuberculosis-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.MethodsWe 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.ResultsWe 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.ConclusionOur 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. |
| first_indexed | 2024-12-18T02:51:11Z |
| format | Article |
| id | doaj.art-883059b1d1d449b19ae0435ec13f6847 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-18T02:51:11Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-883059b1d1d449b19ae0435ec13f68472022-12-21T21:23:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-04-011310.3389/fimmu.2022.873985873985Frequency 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 DiseaseRafael Tibúrcio0Rafael Tibúrcio1Rafael Tibúrcio2Gopalan Narendran3Beatriz Barreto-Duarte4Beatriz Barreto-Duarte5Beatriz Barreto-Duarte6Beatriz Barreto-Duarte7Artur T. L. Queiroz8Artur T. L. Queiroz9Mariana Araújo-Pereira10Mariana Araújo-Pereira11Mariana Araújo-Pereira12Selvaraj Anbalagan13Kaustuv Nayak14Kaustuv Nayak15Narayanan Ravichandran16Rajasekaran Subramani17Lis R. V. Antonelli18Kumar Satagopan19Komathi Anbalagan20Brian O. Porter21Alan Sher22Soumya Swaminathan23Irini Sereti24Bruno B. Andrade25Bruno B. Andrade26Bruno B. Andrade27Bruno B. Andrade28Bruno B. Andrade29Bruno B. Andrade30Bruno B. Andrade31Bruno B. Andrade32Laboratório de Inflamação e Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilMultinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia, Salvador, BrazilDepartment of Clinical Research, National Institute for Research in Tuberculosis, Chennai, IndiaLaboratório de Inflamação e Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilMultinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, BrazilCurso de Medicina, Universidade Salvador (UNIFACS), Salvador, BrazilPrograma de Pós-Graduação em Clínica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilMultinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, BrazilCenter of Data and Knowledge Integration for Health (CIDACS), Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilLaboratório de Inflamação e Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilMultinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia, Salvador, BrazilDepartment of Clinical Research, National Institute for Research in Tuberculosis, Chennai, IndiaDepartment of Clinical Research, National Institute for Research in Tuberculosis, Chennai, IndiaICGEB-Emory Vaccine Centre, International Centre for Genetic Engineering and Biotechnology, New Delhi, IndiaGovernment Hospital of Thoracic Medicine, Chennai, IndiaDepartment of Clinical Research, National Institute for Research in Tuberculosis, Chennai, India0Laboratório de Biologia e Imunologia de Doenças Infecciosas e Parasitárias, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, BrazilGovernment Hospital of Thoracic Medicine, Chennai, IndiaGovernment Hospital of Thoracic Medicine, Chennai, India1HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States2Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesDepartment of Clinical Research, National Institute for Research in Tuberculosis, Chennai, India1HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesLaboratório de Inflamação e Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilMultinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia, Salvador, BrazilCurso de Medicina, Universidade Salvador (UNIFACS), Salvador, BrazilPrograma de Pós-Graduação em Clínica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil3Wellcome Trust Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa4Curso de Medicina, Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador, Brazil5Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United StatesBackgroundTuberculosis-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.MethodsWe 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.ResultsWe 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.873985/fullTB-IRISimmunologic memoryCD8+ T cellsnaïve lymphocytesM. tuberculosis infection |
| spellingShingle | Rafael Tibúrcio Rafael Tibúrcio Rafael Tibúrcio Gopalan Narendran Beatriz Barreto-Duarte Beatriz Barreto-Duarte Beatriz Barreto-Duarte Beatriz Barreto-Duarte Artur T. L. Queiroz Artur T. L. Queiroz Mariana Araújo-Pereira Mariana Araújo-Pereira Mariana Araújo-Pereira Selvaraj Anbalagan Kaustuv Nayak Kaustuv Nayak Narayanan Ravichandran Rajasekaran Subramani Lis R. V. Antonelli Kumar Satagopan Komathi Anbalagan Brian O. Porter Alan Sher Soumya Swaminathan Irini Sereti Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade 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 Frontiers in Immunology TB-IRIS immunologic memory CD8+ T cells naïve lymphocytes M. tuberculosis infection |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | TB-IRIS immunologic memory CD8+ T cells naïve lymphocytes M. tuberculosis infection |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.873985/full |
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