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Invariant Natural Killer T cell dynamics in HIV-associated tuberculosis

Invariant Natural Killer T cell dynamics in HIV-associated tuberculosis
Invariant Natural Killer T cell dynamics in HIV-associated tuberculosis
Rationale: uberculosis (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.
1058-4838
1865-1874
Walker, Naomi
32c9c8b8-6c1d-4439-8315-22d019ca7020
Opondo, Charles
cbb57831-0778-41ab-9d20-5b134fac103f
Meintjes, Graeme
6ba420af-cfb0-412b-b4a4-2749517cd0a2
Jhilmeet, Nishta
1bebeca8-d787-4d85-a7a4-4a3427a338fe
Friedland, Jon
ba98420c-ce9e-408c-9a60-ea58f08ece0b
Elkington, Paul
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Wilkinson, Robert
813aead9-5e18-481a-9dd5-052d31121b78
Wilkinson, Katalin
a5148f73-59fb-4076-bffb-ac27f77ac265
Walker, Naomi
32c9c8b8-6c1d-4439-8315-22d019ca7020
Opondo, Charles
cbb57831-0778-41ab-9d20-5b134fac103f
Meintjes, Graeme
6ba420af-cfb0-412b-b4a4-2749517cd0a2
Jhilmeet, Nishta
1bebeca8-d787-4d85-a7a4-4a3427a338fe
Friedland, Jon
ba98420c-ce9e-408c-9a60-ea58f08ece0b
Elkington, Paul
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Wilkinson, Robert
813aead9-5e18-481a-9dd5-052d31121b78
Wilkinson, Katalin
a5148f73-59fb-4076-bffb-ac27f77ac265

Walker, Naomi, Opondo, Charles, Meintjes, Graeme, Jhilmeet, Nishta, Friedland, Jon, Elkington, Paul, Wilkinson, Robert and Wilkinson, Katalin (2020) Invariant Natural Killer T cell dynamics in HIV-associated tuberculosis. Clinical Infectious Diseases, 70 (9), 1865-1874. (doi:10.1093/cid/ciz501).

Record type: Article

Abstract

Rationale: uberculosis (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.

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More information

Accepted/In Press date: 11 June 2019
e-pub ahead of print date: 12 June 2019
Published date: 1 May 2020

Identifiers

Local EPrints ID: 431836
URI: http://eprints.soton.ac.uk/id/eprint/431836
ISSN: 1058-4838
PURE UUID: 5672fc90-8589-4edf-b62f-8546b335fd46
ORCID for Paul Elkington: ORCID iD orcid.org/0000-0003-0390-0613

Catalogue record

Date deposited: 19 Jun 2019 16:30
Last modified: 26 Nov 2021 05:14

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Contributors

Author: Naomi Walker
Author: Charles Opondo
Author: Graeme Meintjes
Author: Nishta Jhilmeet
Author: Jon Friedland
Author: Paul Elkington ORCID iD
Author: Robert Wilkinson
Author: Katalin Wilkinson

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