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@article{Walker:2020:cid/ciz501,
author = {Walker, NF and Opondo, C and Meintjes, GA and Jhilmeet, N and Friedland, J and Elkington, PT and Wilkinson, RJ and Wilkinson, KA},
doi = {cid/ciz501},
journal = {Clinical Infectious Diseases},
pages = {1865--1874},
title = {Invariant Natural Killer T cell dynamics in HIV-associated tuberculosis},
url = {http://dx.doi.org/10.1093/cid/ciz501},
volume = {70},
year = {2020}
}

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TY  - JOUR
AB  - RationaleTuberculosis (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.ObjectivesWe investigated the hypothesis that invariant Natural Killer T (iNKT) cells contribute to innate immune dysfunction associated with TB-IRIS.MethodsIn 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 resultsCirculating 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.ConclusionsReduced 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.
AU  - Walker,NF
AU  - Opondo,C
AU  - Meintjes,GA
AU  - Jhilmeet,N
AU  - Friedland,J
AU  - Elkington,PT
AU  - Wilkinson,RJ
AU  - Wilkinson,KA
DO  - cid/ciz501
EP  - 1874
PY  - 2020///
SN  - 1058-4838
SP  - 1865
TI  - Invariant Natural Killer T cell dynamics in HIV-associated tuberculosis
T2  - Clinical Infectious Diseases
UR  - http://dx.doi.org/10.1093/cid/ciz501
UR  - http://hdl.handle.net/10044/1/71533
VL  - 70
ER  -

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