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Differential expression of CXCR3 and CCR6 on CD4+ T-lymphocytes with distinct memory phenotypes characterizes tuberculosis-associated immune reconstitution inflammatory syndrome.

ABSTRACT: Immune reconstitution inflammatory syndrome (IRIS) occurs in up to 40% of individuals co-infected with pulmonary tuberculosis (PTB) and HIV, primarily upon antiretroviral therapy (ART) initiation. Phenotypic changes in T-cells during TB-IRIS and their relationship with systemic inflammation are not fully understood. In this prospective cohort study, we followed 48 HIV-positive patients with PTB from South India before and after ART initiation, examining T-lymphocyte subsets and inflammatory biomarkers in peripheral blood. Quantification of naïve (CD27+CD45RO-) as well as effector memory CD4+ T cells (CD27-CD45RO+) at weeks 2-6 after ART initiation could distinguish TB-IRIS from non-IRIS individuals. Additional analyses revealed that ART reconstituted different quantities of CD4+ T lymphocyte subsets with preferential expansion of CXCR3+ CCR6- cells in TB-IRIS patients. Moreover, there was an expansion and functional restoration of central memory (CD27+CD45RO+) CXCR3+CCR6- CD4+ lymphocytes and corresponding cytokines, with reduction in CXCR3-CCR6+ cells after ART initiation only in those who developed TB-IRIS. Together, these observations trace a detailed picture of CD4+ T cell subsets tightly associated with IRIS, which may serve as targets for prophylactic and/or therapeutic interventions in the future.

SUBMITTER: Silveira-Mattos PS

PROVIDER: S-EPMC6365576 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Differential expression of CXCR3 and CCR6 on CD4<sup>+</sup> T-lymphocytes with distinct memory phenotypes characterizes tuberculosis-associated immune reconstitution inflammatory syndrome.

Silveira-Mattos Paulo S PS Narendran Gopalan G Akrami Kevan K Fukutani Kiyoshi F KF Anbalagan Selvaraj S Nayak Kaustuv K Subramanyam Sudha S Subramani Rajasekaran R Vinhaes Caian L CL Souza Deivide Oliveira-de DO Antonelli Lis R LR Satagopan Kumar K Porter Brian O BO Sher Alan A Swaminathan Soumya S Sereti Irini I Andrade Bruno B BB

Scientific reports 20190206 1

Immune reconstitution inflammatory syndrome (IRIS) occurs in up to 40% of individuals co-infected with pulmonary tuberculosis (PTB) and HIV, primarily upon antiretroviral therapy (ART) initiation. Phenotypic changes in T-cells during TB-IRIS and their relationship with systemic inflammation are not fully understood. In this prospective cohort study, we followed 48 HIV-positive patients with PTB from South India before and after ART initiation, examining T-lymphocyte subsets and inflammatory biom ...[more]

PMID: 30728405

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Project 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.

Dataset Information

Differential expression of CXCR3 and CCR6 on CD4+ T-lymphocytes with distinct memory phenotypes characterizes tuberculosis-associated immune reconstitution inflammatory syndrome.

Publications

Differential expression of CXCR3 and CCR6 on CD4<sup>+</sup> T-lymphocytes with distinct memory phenotypes characterizes tuberculosis-associated immune reconstitution inflammatory syndrome.

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