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

Differential expression of CXCR3 and CCR6 on CD4+ T-lymphocytes with distinct memory phenotypes characterizes tuberculosis-associated immune reconstitution inflammatory syndrome. Silveira-Mattos, P. S, Narendran, G., Akrami, K., Fukutani, K. F, Anbalagan, S., Nayak, K., Subramanyam, S., Subramani, R., Vinhaes, C. L, Souza, D. O., Antonelli, L. R, Satagopan, K., Porter, B. O, Sher, A., Swaminathan, S., Sereti, I., & Andrade, B. B Scientific Reports, 9(1):1502, Nature Publishing Group, dec, 2019.

Paper doi abstract bibtex

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.

@article{Silveira-Mattos2019,
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 na{\"{i}}ve (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.},
author = {Silveira-Mattos, Paulo S and Narendran, Gopalan and Akrami, Kevan and Fukutani, Kiyoshi F and Anbalagan, Selvaraj and Nayak, Kaustuv and Subramanyam, Sudha and Subramani, Rajasekaran and Vinhaes, Caian L and Souza, Deivide Oliveira-de and Antonelli, Lis R and Satagopan, Kumar and Porter, Brian O and Sher, Alan and Swaminathan, Soumya and Sereti, Irini and Andrade, Bruno B},
doi = {10.1038/s41598-018-37846-3},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Silveira-Mattos et al. - 2019 - Differential expression of CXCR3 and CCR6 on CD4 T-lymphocytes with distinct memory phenotypes character.pdf:pdf},
journal = {Scientific Reports},
keywords = {OA,fund{\_}not{\_}ack,original},
mendeley-tags = {OA,fund{\_}not{\_}ack,original},
month = {dec},
number = {1},
pages = {1502},
pmid = {30728405},
publisher = {Nature Publishing Group},
title = {{Differential expression of CXCR3 and CCR6 on CD4+ T-lymphocytes with distinct memory phenotypes characterizes tuberculosis-associated immune reconstitution inflammatory syndrome}},
url = {http://www.nature.com/articles/s41598-018-37846-3},
volume = {9},
year = {2019}
}

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