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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.
- Source :
-
Scientific reports [Sci Rep] 2019 Feb 06; Vol. 9 (1), pp. 1502. Date of Electronic Publication: 2019 Feb 06. - Publication Year :
- 2019
-
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 <superscript>+</superscript> CD45RO <superscript>-</superscript> ) as well as effector memory CD4 <superscript>+</superscript> T cells (CD27 <superscript>-</superscript> CD45RO <superscript>+</superscript> ) 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 <superscript>+</superscript> T lymphocyte subsets with preferential expansion of CXCR3 <superscript>+</superscript> CCR6 <superscript>-</superscript> cells in TB-IRIS patients. Moreover, there was an expansion and functional restoration of central memory (CD27 <superscript>+</superscript> CD45RO <superscript>+</superscript> ) CXCR3 <superscript>+</superscript> CCR6 <superscript>-</superscript> CD4 <superscript>+</superscript> lymphocytes and corresponding cytokines, with reduction in CXCR3 <superscript>-</superscript> CCR6 <superscript>+</superscript> cells after ART initiation only in those who developed TB-IRIS. Together, these observations trace a detailed picture of CD4 <superscript>+</superscript> T cell subsets tightly associated with IRIS, which may serve as targets for prophylactic and/or therapeutic interventions in the future.
- Subjects :
- Adult
Aged
Anti-Retroviral Agents administration & dosage
Anti-Retroviral Agents adverse effects
Anti-Retroviral Agents immunology
CD4-Positive T-Lymphocytes metabolism
Cohort Studies
Coinfection immunology
Coinfection parasitology
Coinfection virology
Female
HIV Infections drug therapy
HIV Infections parasitology
Humans
Immune Reconstitution Inflammatory Syndrome chemically induced
Immunologic Memory drug effects
Male
Middle Aged
Prospective Studies
Randomized Controlled Trials as Topic
Receptors, CCR6 biosynthesis
Receptors, CCR6 genetics
Receptors, CXCR3 genetics
T-Lymphocyte Subsets drug effects
T-Lymphocyte Subsets immunology
Tuberculosis, Pulmonary drug therapy
Tuberculosis, Pulmonary virology
CD4-Positive T-Lymphocytes immunology
HIV Infections immunology
Immune Reconstitution Inflammatory Syndrome immunology
Receptors, CCR6 immunology
Receptors, CXCR3 biosynthesis
Receptors, CXCR3 immunology
Tuberculosis, Pulmonary immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 30728405
- Full Text :
- https://doi.org/10.1038/s41598-018-37846-3