Invariant Natural Killer T cell dynamics in HIV-associated tuberculosis

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Title: Invariant Natural Killer T cell dynamics in HIV-associated tuberculosis
Authors: Walker, NF
Opondo, C
Meintjes, GA
Jhilmeet, N
Friedland, J
Elkington, PT
Wilkinson, RJ
Wilkinson, KA
Item Type: Journal Article
Abstract: Rationale Tuberculosis (TB) is the leading cause of mortality and morbidity in people living with HIV infection. HIV-infected patients with TB disease are at risk of the paradoxical TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) when they commence anti-retroviral therapy. However, the pathophysiology is incompletely understood and specific therapy is lacking. Objectives We investigated the hypothesis that invariant Natural Killer T (iNKT) cells contribute to innate immune dysfunction associated with TB-IRIS. Methods In a cross-sectional study of 101 HIV-infected and -uninfected South African patients with active TB and controls, iNKT cells were enumerated using α-galactosylceramide-loaded CD1d tetramers and subsequently functionally characterised by flow cytometry. In a second study of 49 HIV-1-infected TB patients commencing anti-retroviral therapy, iNKT cells in TB-IRIS patients with non-IRIS controls were compared longitudinally. Measurements and main results Circulating iNKT cells were reduced in HIV-1 infection, most significantly the CD4+ subset, which was inversely associated with HIV-1 viral load. iNKT cells in HIV-associated TB had increased surface CD107a expression, indicating cytotoxic degranulation. Relatively increased iNKT cell frequency in HIV-infected patients with active TB was associated with development of TB-IRIS following anti-retroviral therapy initiation. iNKT cells in TB-IRIS were CD4+CD8- subset deplete and degranulated around the time of TB-IRIS onset. Conclusions Reduced iNKT cell CD4+ subsets as a result of HIV-1 infection may skew iNKT cell functionality towards cytotoxicity. Increased CD4- cytotoxic iNKT cells may contribute to immunopathology in TB-IRIS.
Issue Date: 12-Jun-2019
Date of Acceptance: 4-Jun-2019
URI: http://hdl.handle.net/10044/1/71533
DOI: https://dx.doi.org/10.1093/cid/ciz501
ISSN: 1058-4838
Publisher: Oxford University Press (OUP)
Journal / Book Title: Clinical Infectious Diseases
Copyright Statement: © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Wellcome Trust
Wellcome Trust
Funder's Grant Number: 094000/Z/10/Z
104803/Z/14/Z
Keywords: HIV
innate
invariant Natural Killer T cell
paradoxical immune reconstitution inflammatory syndrome (IRIS)
tuberculosis
06 Biological Sciences
11 Medical and Health Sciences
Microbiology
Publication Status: Published online
Online Publication Date: 2019-06-12
Appears in Collections:Department of Medicine



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