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

BACKGROUND: 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 inflammati...

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Autores principales: Tibúrcio, Rafael, Narendran, Gopalan, Barreto-Duarte, Beatriz, Queiroz, Artur T. L., Araújo-Pereira, Mariana, Anbalagan, Selvaraj, Nayak, Kaustuv, Ravichandran, Narayanan, Subramani, Rajasekaran, Antonelli, Lis R. V., Satagopan, Kumar, Anbalagan, Komathi, Porter, Brian O., Sher, Alan, Swaminathan, Soumya, Sereti, Irini, Andrade, Bruno B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011055/
https://www.ncbi.nlm.nih.gov/pubmed/35432354
http://dx.doi.org/10.3389/fimmu.2022.873985
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author Tibúrcio, Rafael
Narendran, Gopalan
Barreto-Duarte, Beatriz
Queiroz, Artur T. L.
Araújo-Pereira, Mariana
Anbalagan, Selvaraj
Nayak, Kaustuv
Ravichandran, Narayanan
Subramani, Rajasekaran
Antonelli, Lis R. V.
Satagopan, Kumar
Anbalagan, Komathi
Porter, Brian O.
Sher, Alan
Swaminathan, Soumya
Sereti, Irini
Andrade, Bruno B.
author_facet Tibúrcio, Rafael
Narendran, Gopalan
Barreto-Duarte, Beatriz
Queiroz, Artur T. L.
Araújo-Pereira, Mariana
Anbalagan, Selvaraj
Nayak, Kaustuv
Ravichandran, Narayanan
Subramani, Rajasekaran
Antonelli, Lis R. V.
Satagopan, Kumar
Anbalagan, Komathi
Porter, Brian O.
Sher, Alan
Swaminathan, Soumya
Sereti, Irini
Andrade, Bruno B.
author_sort Tibúrcio, Rafael
collection PubMed
description BACKGROUND: 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.
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spelling pubmed-90110552022-04-16 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 Tibúrcio, Rafael Narendran, Gopalan Barreto-Duarte, Beatriz Queiroz, Artur T. L. Araújo-Pereira, Mariana Anbalagan, Selvaraj Nayak, Kaustuv Ravichandran, Narayanan Subramani, Rajasekaran Antonelli, Lis R. V. Satagopan, Kumar Anbalagan, Komathi Porter, Brian O. Sher, Alan Swaminathan, Soumya Sereti, Irini Andrade, Bruno B. Front Immunol Immunology BACKGROUND: 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. Frontiers Media S.A. 2022-04-01 /pmc/articles/PMC9011055/ /pubmed/35432354 http://dx.doi.org/10.3389/fimmu.2022.873985 Text en Copyright © 2022 Tibúrcio, Narendran, Barreto-Duarte, Queiroz, Araújo-Pereira, Anbalagan, Nayak, Ravichandran, Subramani, Antonelli, Satagopan, Anbalagan, Porter, Sher, Swaminathan, Sereti and Andrade https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Tibúrcio, Rafael
Narendran, Gopalan
Barreto-Duarte, Beatriz
Queiroz, Artur T. L.
Araújo-Pereira, Mariana
Anbalagan, Selvaraj
Nayak, Kaustuv
Ravichandran, Narayanan
Subramani, Rajasekaran
Antonelli, Lis R. V.
Satagopan, Kumar
Anbalagan, Komathi
Porter, Brian O.
Sher, Alan
Swaminathan, Soumya
Sereti, Irini
Andrade, Bruno B.
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 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 Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011055/
https://www.ncbi.nlm.nih.gov/pubmed/35432354
http://dx.doi.org/10.3389/fimmu.2022.873985
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