Early and non-reversible decrease of CD161++/MAIT cells in HIV infection

Cormac Cosgrove; James E Ussher; Andri Rauch; Kathleen Gartner; Ayako Kurioka; Michael H. Huhn; Krista Adelmann; Yu-Hoi Kang; Joannah R Fergusson; Peter Simmonds; Philip Goulder; Ted H Hansen; J. Fox; HF Gunthard; Nina Khanna; Fiona Powrie; Alan  Steel; Brian Gazzard; Rodney E Phillips; John Frater; Holm Uhlig; Paul Klenerman

doi:10.1182/blood-2012-06-436436

Early and non-reversible decrease of CD161++/MAIT cells in HIV infection

Cormac Cosgrove, James E Ussher, Andri Rauch, Kathleen Gartner, Ayako Kurioka, Michael H. Huhn, Krista Adelmann, Yu-Hoi Kang, Joannah R Fergusson, Peter Simmonds, Philip Goulder, Ted H Hansen, J. Fox, HF Gunthard, Nina Khanna, Fiona Powrie, Alan Steel, Brian Gazzard, Rodney E Phillips, John FraterHolm Uhlig, Paul Klenerman

Research output: Contribution to journal › Article › peer-review

Abstract

HIV infection is associated with immune dysfunction, perturbation of immune-cell subsets and opportunistic infections. CD161++CD8+T-cells are a tissue-infiltrating population that produce IL17A, IL22, IFNγ and TNFα, cytokines important in mucosal immunity. In adults they dominantly express the semi-invariant TCR Vα7.2, the canonical feature of Mucosal Associated Invariant T-cells (MAIT) and have been recently implicated in host defence against pathogens. We analyzed the frequency and function of CD161++/MAIT-cells in peripheral blood and tissue from patients with early-stage or chronic-stage HIV infection. We show that the CD161++/MAIT-cell population is significantly decreased in early HIV infection and fails to recover despite otherwise successful treatment. We provide evidence that CD161++/MAIT-cells are not preferentially infected but may be depleted through diverse mechanisms including accumulation in tissues and activation-induced cell death. This loss may impact on mucosal defence and could be important in susceptibility to specific opportunistic infections in HIV.

Original language	English
Pages (from-to)	951-61
Number of pages	11
Journal	Blood
Volume	121
Issue number	6
Early online date	18 Dec 2012
DOIs	https://doi.org/10.1182/blood-2012-06-436436
Publication status	Published - 7 Feb 2013

Keywords / Materials (for Non-textual outputs)

HIV Infections

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10.1182/blood-2012-06-436436

http://bloodjournal.hematologylibrary.org/content/early/2012/12/18/blood-2012-06-436436

Infection of CD8 lymphocytes by HIV -1
Simmonds, P. (Principal Investigator)
MRC
17/02/09 → 30/04/12
Project: Research

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Cosgrove, C., Ussher, J. E., Rauch, A., Gartner, K., Kurioka, A., Huhn, M. H., Adelmann, K., Kang, Y.-H., Fergusson, J. R., Simmonds, P., Goulder, P., Hansen, T. H., Fox, J., Gunthard, HF., Khanna, N., Powrie, F., Steel, A., Gazzard, B., Phillips, R. E., ... Klenerman, P. (2013). Early and non-reversible decrease of CD161++/MAIT cells in HIV infection. Blood, 121(6), 951-61. https://doi.org/10.1182/blood-2012-06-436436

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title = "Early and non-reversible decrease of CD161++/MAIT cells in HIV infection",

abstract = "HIV infection is associated with immune dysfunction, perturbation of immune-cell subsets and opportunistic infections. CD161++CD8+T-cells are a tissue-infiltrating population that produce IL17A, IL22, IFNγ and TNFα, cytokines important in mucosal immunity. In adults they dominantly express the semi-invariant TCR Vα7.2, the canonical feature of Mucosal Associated Invariant T-cells (MAIT) and have been recently implicated in host defence against pathogens. We analyzed the frequency and function of CD161++/MAIT-cells in peripheral blood and tissue from patients with early-stage or chronic-stage HIV infection. We show that the CD161++/MAIT-cell population is significantly decreased in early HIV infection and fails to recover despite otherwise successful treatment. We provide evidence that CD161++/MAIT-cells are not preferentially infected but may be depleted through diverse mechanisms including accumulation in tissues and activation-induced cell death. This loss may impact on mucosal defence and could be important in susceptibility to specific opportunistic infections in HIV.",

keywords = "HIV Infections",

author = "Cormac Cosgrove and Ussher, \{James E\} and Andri Rauch and Kathleen Gartner and Ayako Kurioka and Huhn, \{Michael H.\} and Krista Adelmann and Yu-Hoi Kang and Fergusson, \{Joannah R\} and Peter Simmonds and Philip Goulder and Hansen, \{Ted H\} and J. Fox and HF Gunthard and Nina Khanna and Fiona Powrie and Alan Steel and Brian Gazzard and Phillips, \{Rodney E\} and John Frater and Holm Uhlig and Paul Klenerman",

year = "2013",

month = feb,

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doi = "10.1182/blood-2012-06-436436",

language = "English",

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Cosgrove, C, Ussher, JE, Rauch, A, Gartner, K, Kurioka, A, Huhn, MH, Adelmann, K, Kang, Y-H, Fergusson, JR, Simmonds, P, Goulder, P, Hansen, TH, Fox, J, Gunthard, HF, Khanna, N, Powrie, F, Steel, A, Gazzard, B, Phillips, RE, Frater, J, Uhlig, H & Klenerman, P 2013, 'Early and non-reversible decrease of CD161++/MAIT cells in HIV infection', Blood, vol. 121, no. 6, pp. 951-61. https://doi.org/10.1182/blood-2012-06-436436

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AU - Cosgrove, Cormac

AU - Ussher, James E

AU - Rauch, Andri

AU - Gartner, Kathleen

AU - Kurioka, Ayako

AU - Huhn, Michael H.

AU - Adelmann, Krista

AU - Kang, Yu-Hoi

AU - Fergusson, Joannah R

AU - Simmonds, Peter

AU - Goulder, Philip

AU - Hansen, Ted H

AU - Fox, J.

AU - Gunthard, HF

AU - Khanna, Nina

AU - Powrie, Fiona

AU - Steel, Alan

AU - Gazzard, Brian

AU - Phillips, Rodney E

AU - Frater, John

AU - Uhlig, Holm

AU - Klenerman, Paul

PY - 2013/2/7

Y1 - 2013/2/7

N2 - HIV infection is associated with immune dysfunction, perturbation of immune-cell subsets and opportunistic infections. CD161++CD8+T-cells are a tissue-infiltrating population that produce IL17A, IL22, IFNγ and TNFα, cytokines important in mucosal immunity. In adults they dominantly express the semi-invariant TCR Vα7.2, the canonical feature of Mucosal Associated Invariant T-cells (MAIT) and have been recently implicated in host defence against pathogens. We analyzed the frequency and function of CD161++/MAIT-cells in peripheral blood and tissue from patients with early-stage or chronic-stage HIV infection. We show that the CD161++/MAIT-cell population is significantly decreased in early HIV infection and fails to recover despite otherwise successful treatment. We provide evidence that CD161++/MAIT-cells are not preferentially infected but may be depleted through diverse mechanisms including accumulation in tissues and activation-induced cell death. This loss may impact on mucosal defence and could be important in susceptibility to specific opportunistic infections in HIV.

AB - HIV infection is associated with immune dysfunction, perturbation of immune-cell subsets and opportunistic infections. CD161++CD8+T-cells are a tissue-infiltrating population that produce IL17A, IL22, IFNγ and TNFα, cytokines important in mucosal immunity. In adults they dominantly express the semi-invariant TCR Vα7.2, the canonical feature of Mucosal Associated Invariant T-cells (MAIT) and have been recently implicated in host defence against pathogens. We analyzed the frequency and function of CD161++/MAIT-cells in peripheral blood and tissue from patients with early-stage or chronic-stage HIV infection. We show that the CD161++/MAIT-cell population is significantly decreased in early HIV infection and fails to recover despite otherwise successful treatment. We provide evidence that CD161++/MAIT-cells are not preferentially infected but may be depleted through diverse mechanisms including accumulation in tissues and activation-induced cell death. This loss may impact on mucosal defence and could be important in susceptibility to specific opportunistic infections in HIV.

KW - HIV Infections

U2 - 10.1182/blood-2012-06-436436

DO - 10.1182/blood-2012-06-436436

M3 - Article

C2 - 23255555

SN - 0006-4971

VL - 121

SP - 951

EP - 961

JO - Blood

JF - Blood

IS - 6

ER -

Early and non-reversible decrease of CD161++/MAIT cells in HIV infection

Abstract

Keywords / Materials (for Non-textual outputs)

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Projects

Infection of CD8 lymphocytes by HIV -1

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