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

Immune reconstitution infammatory 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 infammation 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 infammatory biomarkers in peripheral blood. Quantifcation of naïve (CD27+CD45RO−) as well as efector 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 diferent 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.

• Data de Publicação: 06/02/2019
• Autores: PauloS.Silveira-Mattos, GopalanNarendran, KevanAkrami, Kiyoshi F. Fukutani, SelvarajAnbalagan, Kaustuv Nayak, SudhaSubramanyam, RajasekaranSubramani, Caian L.Vinhaes, DeivideOliveira-deSouza, LisR.Antonelli, KumarSatagopan, BrianO.Porter, AlanSher, SoumyaSwaminathan, IriniSereti & BrunoB.Andrade