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Impaired natural killer cell responses are associated with loss of the highly activated NKG2A+CD57+CD56dim subset in HIV-1 subtype D infection in Uganda

Objective: Of the predominant HIV-1 subtypes in Uganda, subtype D infection confers a worse prognosis. HIV-1 infection causes perturbations to natural killer (NK) cells, and yet these cells can exert immune pressure on the virus and influence clinical outcome. Here, we studied NK cell activation and... Full description

Journal Title: AIDS (London) 2014, Vol.28 (9), p.1273-1278
Main Author: NALUYIMA, Prossy
Other Authors: ELLER, Michael A , SANDBERG, Johan K , LAEYENDECKER, Oliver , QUINN, Thomas C , SERWADDA, David , SEWANKAMBO, Nelson K , GRAY, Ronald H , MICHAEL, Nelson L , WABWIRE-MANGEN, Fred , ROBB, Merlin L
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Hagerstown, MD: Lippincott Williams & Wilkins
ID: ISSN: 0269-9370
Link: http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28603177
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recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4032214
title: Impaired natural killer cell responses are associated with loss of the highly activated NKG2A+CD57+CD56dim subset in HIV-1 subtype D infection in Uganda
format: Article
creator:
  • NALUYIMA, Prossy
  • ELLER, Michael A
  • SANDBERG, Johan K
  • LAEYENDECKER, Oliver
  • QUINN, Thomas C
  • SERWADDA, David
  • SEWANKAMBO, Nelson K
  • GRAY, Ronald H
  • MICHAEL, Nelson L
  • WABWIRE-MANGEN, Fred
  • ROBB, Merlin L
subjects:
  • AIDS
  • Basic Science
  • Biological and medical sciences
  • CD57
  • Concise Communication
  • HIV-1
  • Human immunodeficiency virus
  • Human immunodeficiency virus 1
  • Human viral diseases
  • immune activation
  • Immunodeficiencies
  • Immunodeficiencies. Immunoglobulinopathies
  • Immunopathology
  • Infectious diseases
  • Lentivirus
  • Medical sciences
  • natural killer cells
  • NKG2A
  • Retroviridae
  • subtype D
  • Viral diseases
  • Viral diseases of the lymphoid tissue and the blood. Aids
ispartof: AIDS (London), 2014, Vol.28 (9), p.1273-1278
description: Objective: Of the predominant HIV-1 subtypes in Uganda, subtype D infection confers a worse prognosis. HIV-1 infection causes perturbations to natural killer (NK) cells, and yet these cells can exert immune pressure on the virus and influence clinical outcome. Here, we studied NK cell activation and function in Ugandans with chronic untreated HIV-1 subtype D infection in comparison to uninfected community matched controls. Methods: Cryopreserved peripheral blood mononuclear cells (PBMCs) from 42 HIV-infected individuals and 28 HIV-negative controls were analysed using eight-colour flow cytometry. NK cell surface expression of CD16, CD56, CD57, HLA-DR and NKG2A were used to investigate activation, maturation and differentiation status. NK cell function was evaluated by measuring interferon-gamma (IFN gamma ) production in response to K562 cells, or interleukin (IL)-12 and IL-18. Results: CD56dim NK cells from HIV-infected individuals produced less IFN gamma in response to IL-12 and IL-18 than did CD56dim NK cells from uninfected controls. Infected individuals had lower levels of CD56 super(dim) NK cells coexpressing the differentiation markers NKG2A and CD57 than controls. In addition, their NKG2A+CD57+ CD56 super(dim) NK cells displayed elevated activation levels as assessed by HLA-DR expression. Cytokine-induced IFN gamma production correlated directly with coexpression of CD57 and NKG2A on CD56 super(dim) NK cells. Conclusion: HIV-1 subtype D infection is associated with impaired NK cell responsiveness to cytokines, decline of the NKG2A super(+) CD57 super(+) CD56dim NK cell subset, as well as elevated activation in this subset. These alterations within the NK cell compartment may contribute to immunopathogenesis of HIV-1 subtype D infection in Ugandans.
language: eng
source:
identifier: ISSN: 0269-9370
fulltext: no_fulltext
issn:
  • 0269-9370
  • 1473-5571
url: Link


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titleImpaired natural killer cell responses are associated with loss of the highly activated NKG2A+CD57+CD56dim subset in HIV-1 subtype D infection in Uganda
creatorNALUYIMA, Prossy ; ELLER, Michael A ; SANDBERG, Johan K ; LAEYENDECKER, Oliver ; QUINN, Thomas C ; SERWADDA, David ; SEWANKAMBO, Nelson K ; GRAY, Ronald H ; MICHAEL, Nelson L ; WABWIRE-MANGEN, Fred ; ROBB, Merlin L
creatorcontribNALUYIMA, Prossy ; ELLER, Michael A ; SANDBERG, Johan K ; LAEYENDECKER, Oliver ; QUINN, Thomas C ; SERWADDA, David ; SEWANKAMBO, Nelson K ; GRAY, Ronald H ; MICHAEL, Nelson L ; WABWIRE-MANGEN, Fred ; ROBB, Merlin L
descriptionObjective: Of the predominant HIV-1 subtypes in Uganda, subtype D infection confers a worse prognosis. HIV-1 infection causes perturbations to natural killer (NK) cells, and yet these cells can exert immune pressure on the virus and influence clinical outcome. Here, we studied NK cell activation and function in Ugandans with chronic untreated HIV-1 subtype D infection in comparison to uninfected community matched controls. Methods: Cryopreserved peripheral blood mononuclear cells (PBMCs) from 42 HIV-infected individuals and 28 HIV-negative controls were analysed using eight-colour flow cytometry. NK cell surface expression of CD16, CD56, CD57, HLA-DR and NKG2A were used to investigate activation, maturation and differentiation status. NK cell function was evaluated by measuring interferon-gamma (IFN gamma ) production in response to K562 cells, or interleukin (IL)-12 and IL-18. Results: CD56dim NK cells from HIV-infected individuals produced less IFN gamma in response to IL-12 and IL-18 than did CD56dim NK cells from uninfected controls. Infected individuals had lower levels of CD56 super(dim) NK cells coexpressing the differentiation markers NKG2A and CD57 than controls. In addition, their NKG2A+CD57+ CD56 super(dim) NK cells displayed elevated activation levels as assessed by HLA-DR expression. Cytokine-induced IFN gamma production correlated directly with coexpression of CD57 and NKG2A on CD56 super(dim) NK cells. Conclusion: HIV-1 subtype D infection is associated with impaired NK cell responsiveness to cytokines, decline of the NKG2A super(+) CD57 super(+) CD56dim NK cell subset, as well as elevated activation in this subset. These alterations within the NK cell compartment may contribute to immunopathogenesis of HIV-1 subtype D infection in Ugandans.
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subjectAIDS ; Basic Science ; Biological and medical sciences ; CD57 ; Concise Communication ; HIV-1 ; Human immunodeficiency virus ; Human immunodeficiency virus 1 ; Human viral diseases ; immune activation ; Immunodeficiencies ; Immunodeficiencies. Immunoglobulinopathies ; Immunopathology ; Infectious diseases ; Lentivirus ; Medical sciences ; natural killer cells ; NKG2A ; Retroviridae ; subtype D ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids
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descriptionObjective: Of the predominant HIV-1 subtypes in Uganda, subtype D infection confers a worse prognosis. HIV-1 infection causes perturbations to natural killer (NK) cells, and yet these cells can exert immune pressure on the virus and influence clinical outcome. Here, we studied NK cell activation and function in Ugandans with chronic untreated HIV-1 subtype D infection in comparison to uninfected community matched controls. Methods: Cryopreserved peripheral blood mononuclear cells (PBMCs) from 42 HIV-infected individuals and 28 HIV-negative controls were analysed using eight-colour flow cytometry. NK cell surface expression of CD16, CD56, CD57, HLA-DR and NKG2A were used to investigate activation, maturation and differentiation status. NK cell function was evaluated by measuring interferon-gamma (IFN gamma ) production in response to K562 cells, or interleukin (IL)-12 and IL-18. Results: CD56dim NK cells from HIV-infected individuals produced less IFN gamma in response to IL-12 and IL-18 than did CD56dim NK cells from uninfected controls. Infected individuals had lower levels of CD56 super(dim) NK cells coexpressing the differentiation markers NKG2A and CD57 than controls. In addition, their NKG2A+CD57+ CD56 super(dim) NK cells displayed elevated activation levels as assessed by HLA-DR expression. Cytokine-induced IFN gamma production correlated directly with coexpression of CD57 and NKG2A on CD56 super(dim) NK cells. Conclusion: HIV-1 subtype D infection is associated with impaired NK cell responsiveness to cytokines, decline of the NKG2A super(+) CD57 super(+) CD56dim NK cell subset, as well as elevated activation in this subset. These alterations within the NK cell compartment may contribute to immunopathogenesis of HIV-1 subtype D infection in Ugandans.
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titleImpaired natural killer cell responses are associated with loss of the highly activated NKG2A+CD57+CD56dim subset in HIV-1 subtype D infection in Uganda
authorNALUYIMA, Prossy ; ELLER, Michael A ; SANDBERG, Johan K ; LAEYENDECKER, Oliver ; QUINN, Thomas C ; SERWADDA, David ; SEWANKAMBO, Nelson K ; GRAY, Ronald H ; MICHAEL, Nelson L ; WABWIRE-MANGEN, Fred ; ROBB, Merlin L
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10Immunodeficiencies
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atitleImpaired natural killer cell responses are associated with loss of the highly activated NKG2A+CD57+CD56dim subset in HIV-1 subtype D infection in Uganda
jtitleAIDS (London)
date2014
risdate2014
volume28
issue9
spage1273
epage1278
pages1273-1278
issn0269-9370
eissn1473-5571
abstractObjective: Of the predominant HIV-1 subtypes in Uganda, subtype D infection confers a worse prognosis. HIV-1 infection causes perturbations to natural killer (NK) cells, and yet these cells can exert immune pressure on the virus and influence clinical outcome. Here, we studied NK cell activation and function in Ugandans with chronic untreated HIV-1 subtype D infection in comparison to uninfected community matched controls. Methods: Cryopreserved peripheral blood mononuclear cells (PBMCs) from 42 HIV-infected individuals and 28 HIV-negative controls were analysed using eight-colour flow cytometry. NK cell surface expression of CD16, CD56, CD57, HLA-DR and NKG2A were used to investigate activation, maturation and differentiation status. NK cell function was evaluated by measuring interferon-gamma (IFN gamma ) production in response to K562 cells, or interleukin (IL)-12 and IL-18. Results: CD56dim NK cells from HIV-infected individuals produced less IFN gamma in response to IL-12 and IL-18 than did CD56dim NK cells from uninfected controls. Infected individuals had lower levels of CD56 super(dim) NK cells coexpressing the differentiation markers NKG2A and CD57 than controls. In addition, their NKG2A+CD57+ CD56 super(dim) NK cells displayed elevated activation levels as assessed by HLA-DR expression. Cytokine-induced IFN gamma production correlated directly with coexpression of CD57 and NKG2A on CD56 super(dim) NK cells. Conclusion: HIV-1 subtype D infection is associated with impaired NK cell responsiveness to cytokines, decline of the NKG2A super(+) CD57 super(+) CD56dim NK cell subset, as well as elevated activation in this subset. These alterations within the NK cell compartment may contribute to immunopathogenesis of HIV-1 subtype D infection in Ugandans.
copHagerstown, MD
pubLippincott Williams & Wilkins
pmid24959961
doi10.1097/QAD.0000000000000286
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