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.

Publication date: Feb 06, 2019

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 nacEFve (CD27CD45RO) as well as effector memory CD4 T cells (CD27CD45RO) 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 (CD27CD45RO) CXCR3CCR6 CD4 lymphocytes and corresponding cytokines, with reduction in CXCR3CCR6 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.

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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, and Andrade, B.B. Differential expression of CXCR3 and CCR6 on CD4 T-lymphocytes with distinct memory phenotypes characterizes tuberculosis-associated immune reconstitution inflammatory syndrome. 04736. 2019 Sci Rep (9):1.



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