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Interferon gamma (IFN-γ) negative CD4+ and CD8+ T-cells can produce immune mediators in response to viral antigens

Evaluation of antigen-specific T-cell responses to viral antigens is frequently performed on IFN-γ secreting cells. However, T-cells are capable of producing many more functions than just IFN-γ, some of which, like Perforin, are associated with immune protection in HIV-1 disease elite controllers. W... Full description

Journal Title: Vaccine 2019, Vol.37 (1), p.113-122
Main Author: Nakiboneka, Ritah
Other Authors: Mugaba, Susan , Auma, Betty O , Kintu, Christopher , Lindan, Christina , Nanteza, Mary Bridget , Kaleebu, Pontiano , Serwanga, Jennifer
Format: Electronic Article Electronic Article
Language: English
Subjects:
HIV
Quelle: Alma/SFX Local Collection
Publisher: Netherlands: Elsevier Ltd
ID: ISSN: 0264-410X
Link: https://www.ncbi.nlm.nih.gov/pubmed/30459072
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recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6290111
title: Interferon gamma (IFN-γ) negative CD4+ and CD8+ T-cells can produce immune mediators in response to viral antigens
format: Article
creator:
  • Nakiboneka, Ritah
  • Mugaba, Susan
  • Auma, Betty O
  • Kintu, Christopher
  • Lindan, Christina
  • Nanteza, Mary Bridget
  • Kaleebu, Pontiano
  • Serwanga, Jennifer
subjects:
  • Acquired immune deficiency syndrome
  • Adenoviridae
  • Adenoviruses
  • AIDS
  • Antigens
  • Antigens, Viral - immunology
  • Antiretroviral drugs
  • Antiretroviral therapy
  • Apoptosis
  • Article
  • Biological response modifiers
  • CD4 antigen
  • CD4-Positive T-Lymphocytes - immunology
  • CD8 antigen
  • CD8-Positive T-Lymphocytes - immunology
  • cell responses
  • cells
  • Clinical trials
  • Cohort Studies
  • Cross-Sectional Studies
  • Cytokines
  • Disease control
  • ELISpot assay
  • Enzyme-linked immunosorbent assay
  • Enzyme-Linked Immunospot Assay
  • Epidemiology
  • Evaluation
  • Flow Cytometry
  • Health aspects
  • HIV
  • HIV (Viruses)
  • HIV Infections - immunology
  • HIV-1
  • Human immunodeficiency virus
  • Humans
  • IFN-γ negative T-cells
  • Immune response
  • Immunogenicity
  • Immunologic Factors - immunology
  • Interferon
  • Interferon gamma
  • Interferon-gamma - immunology
  • Interleukin 2
  • Interleukin-2 - immunology
  • Leukocytes (mononuclear)
  • Leukocytes, Mononuclear - immunology
  • Lymphocyte Activation
  • Lymphocytes T
  • Medical research
  • Medicine, Experimental
  • Peptides
  • Peptides - immunology
  • Perforin
  • Perforin - immunology
  • Peripheral blood mononuclear cells
  • Phenotypes
  • T cells
  • T-cell responses
  • Tumor Necrosis Factor-alpha - immunology
  • Tumor necrosis factor-TNF
  • Tumor necrosis factor-α
  • Vaccines
  • Viral antigens
  • Viruses
  • γ negative T
  • γ-Interferon
ispartof: Vaccine, 2019, Vol.37 (1), p.113-122
description: Evaluation of antigen-specific T-cell responses to viral antigens is frequently performed on IFN-γ secreting cells. However, T-cells are capable of producing many more functions than just IFN-γ, some of which, like Perforin, are associated with immune protection in HIV-1 disease elite controllers. We evaluated the extent of missed T-cell functions when IFN-γ secretion is used as a surrogate marker for further evaluation of T-cell functions. Intracellular cytokine staining assay and flow cytometry were used to assess peripheral blood mononuclear cells (PBMCs) from 31 HIV-infected ART-naive individuals for the extent to which gated CD4+ and CD8+ IFN-γ producing and non-producing T-cells also secreted IL-2, Perforin, and TNF-α functions. Similarly, the extent of missed virus-specific responses in IFN-γ ELISpot assay negative T-cells from 5 HIV-1 uninfected individuals was evaluated. Cells from HIV-infected individuals were stimulated with pooled consensus group M (Con M) peptides; and those from healthy individuals were stimulated with pooled adenovirus (Ad) peptides. Overall, frequencies of virus-specific IFN-γ secreting CD4+ and CD8+ cells were low. Proportions of IFN-γ negative CD4+ expressing IL-2, Perforin, or TNF-α to Con M were significantly higher (5 of 7 functional profiles) than the corresponding IFN-γ positive CD4+ (0 of 7) T-cell phenotype, p = 0.02; Fisher’s Exact test. Likewise, proportions of CD8+ T-cells expressing other functions were significantly higher in 4 of the 7 IFN-γ negative CD8+ T-cells. Notably, newly stimulated Perforin, identified as Perforin co-expression with IL-2 or TNF-α, was significantly higher in IFN-γ negative CD8+ T-cell than in the positive CD8+ T-cells. Using SEB, lower responses in IFN-γ positive cells were most associated with CD4+ than CD8+ T-cells. These findings suggest that studies evaluating immunogenicity in response to HIV and Adenovirus viral antigens should not only evaluate T-cell responsiveness among IFN-γ producing cells but also among those T-cells that do not express IFN-γ.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0264-410X
fulltext: fulltext
issn:
  • 0264-410X
  • 1873-2518
url: Link


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titleInterferon gamma (IFN-γ) negative CD4+ and CD8+ T-cells can produce immune mediators in response to viral antigens
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creatorNakiboneka, Ritah ; Mugaba, Susan ; Auma, Betty O ; Kintu, Christopher ; Lindan, Christina ; Nanteza, Mary Bridget ; Kaleebu, Pontiano ; Serwanga, Jennifer
creatorcontribNakiboneka, Ritah ; Mugaba, Susan ; Auma, Betty O ; Kintu, Christopher ; Lindan, Christina ; Nanteza, Mary Bridget ; Kaleebu, Pontiano ; Serwanga, Jennifer
descriptionEvaluation of antigen-specific T-cell responses to viral antigens is frequently performed on IFN-γ secreting cells. However, T-cells are capable of producing many more functions than just IFN-γ, some of which, like Perforin, are associated with immune protection in HIV-1 disease elite controllers. We evaluated the extent of missed T-cell functions when IFN-γ secretion is used as a surrogate marker for further evaluation of T-cell functions. Intracellular cytokine staining assay and flow cytometry were used to assess peripheral blood mononuclear cells (PBMCs) from 31 HIV-infected ART-naive individuals for the extent to which gated CD4+ and CD8+ IFN-γ producing and non-producing T-cells also secreted IL-2, Perforin, and TNF-α functions. Similarly, the extent of missed virus-specific responses in IFN-γ ELISpot assay negative T-cells from 5 HIV-1 uninfected individuals was evaluated. Cells from HIV-infected individuals were stimulated with pooled consensus group M (Con M) peptides; and those from healthy individuals were stimulated with pooled adenovirus (Ad) peptides. Overall, frequencies of virus-specific IFN-γ secreting CD4+ and CD8+ cells were low. Proportions of IFN-γ negative CD4+ expressing IL-2, Perforin, or TNF-α to Con M were significantly higher (5 of 7 functional profiles) than the corresponding IFN-γ positive CD4+ (0 of 7) T-cell phenotype, p = 0.02; Fisher’s Exact test. Likewise, proportions of CD8+ T-cells expressing other functions were significantly higher in 4 of the 7 IFN-γ negative CD8+ T-cells. Notably, newly stimulated Perforin, identified as Perforin co-expression with IL-2 or TNF-α, was significantly higher in IFN-γ negative CD8+ T-cell than in the positive CD8+ T-cells. Using SEB, lower responses in IFN-γ positive cells were most associated with CD4+ than CD8+ T-cells. These findings suggest that studies evaluating immunogenicity in response to HIV and Adenovirus viral antigens should not only evaluate T-cell responsiveness among IFN-γ producing cells but also among those T-cells that do not express IFN-γ.
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0ISSN: 0264-410X
1EISSN: 1873-2518
2DOI: 10.1016/j.vaccine.2018.11.024
3PMID: 30459072
languageeng
publisherNetherlands: Elsevier Ltd
subjectAcquired immune deficiency syndrome ; Adenoviridae ; Adenoviruses ; AIDS ; Antigens ; Antigens, Viral - immunology ; Antiretroviral drugs ; Antiretroviral therapy ; Apoptosis ; Article ; Biological response modifiers ; CD4 antigen ; CD4-Positive T-Lymphocytes - immunology ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; cell responses ; cells ; Clinical trials ; Cohort Studies ; Cross-Sectional Studies ; Cytokines ; Disease control ; ELISpot assay ; Enzyme-linked immunosorbent assay ; Enzyme-Linked Immunospot Assay ; Epidemiology ; Evaluation ; Flow Cytometry ; Health aspects ; HIV ; HIV (Viruses) ; HIV Infections - immunology ; HIV-1 ; Human immunodeficiency virus ; Humans ; IFN-γ negative T-cells ; Immune response ; Immunogenicity ; Immunologic Factors - immunology ; Interferon ; Interferon gamma ; Interferon-gamma - immunology ; Interleukin 2 ; Interleukin-2 - immunology ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - immunology ; Lymphocyte Activation ; Lymphocytes T ; Medical research ; Medicine, Experimental ; Peptides ; Peptides - immunology ; Perforin ; Perforin - immunology ; Peripheral blood mononuclear cells ; Phenotypes ; T cells ; T-cell responses ; Tumor Necrosis Factor-alpha - immunology ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; Vaccines ; Viral antigens ; Viruses ; γ negative T ; γ-Interferon
ispartofVaccine, 2019, Vol.37 (1), p.113-122
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1Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
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0Nakiboneka, Ritah
1Mugaba, Susan
2Auma, Betty O
3Kintu, Christopher
4Lindan, Christina
5Nanteza, Mary Bridget
6Kaleebu, Pontiano
7Serwanga, Jennifer
title
0Interferon gamma (IFN-γ) negative CD4+ and CD8+ T-cells can produce immune mediators in response to viral antigens
1Vaccine
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descriptionEvaluation of antigen-specific T-cell responses to viral antigens is frequently performed on IFN-γ secreting cells. However, T-cells are capable of producing many more functions than just IFN-γ, some of which, like Perforin, are associated with immune protection in HIV-1 disease elite controllers. We evaluated the extent of missed T-cell functions when IFN-γ secretion is used as a surrogate marker for further evaluation of T-cell functions. Intracellular cytokine staining assay and flow cytometry were used to assess peripheral blood mononuclear cells (PBMCs) from 31 HIV-infected ART-naive individuals for the extent to which gated CD4+ and CD8+ IFN-γ producing and non-producing T-cells also secreted IL-2, Perforin, and TNF-α functions. Similarly, the extent of missed virus-specific responses in IFN-γ ELISpot assay negative T-cells from 5 HIV-1 uninfected individuals was evaluated. Cells from HIV-infected individuals were stimulated with pooled consensus group M (Con M) peptides; and those from healthy individuals were stimulated with pooled adenovirus (Ad) peptides. Overall, frequencies of virus-specific IFN-γ secreting CD4+ and CD8+ cells were low. Proportions of IFN-γ negative CD4+ expressing IL-2, Perforin, or TNF-α to Con M were significantly higher (5 of 7 functional profiles) than the corresponding IFN-γ positive CD4+ (0 of 7) T-cell phenotype, p = 0.02; Fisher’s Exact test. Likewise, proportions of CD8+ T-cells expressing other functions were significantly higher in 4 of the 7 IFN-γ negative CD8+ T-cells. Notably, newly stimulated Perforin, identified as Perforin co-expression with IL-2 or TNF-α, was significantly higher in IFN-γ negative CD8+ T-cell than in the positive CD8+ T-cells. Using SEB, lower responses in IFN-γ positive cells were most associated with CD4+ than CD8+ T-cells. These findings suggest that studies evaluating immunogenicity in response to HIV and Adenovirus viral antigens should not only evaluate T-cell responsiveness among IFN-γ producing cells but also among those T-cells that do not express IFN-γ.
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0Acquired immune deficiency syndrome
1Adenoviridae
2Adenoviruses
3AIDS
4Antigens
5Antigens, Viral - immunology
6Antiretroviral drugs
7Antiretroviral therapy
8Apoptosis
9Article
10Biological response modifiers
11CD4 antigen
12CD4-Positive T-Lymphocytes - immunology
13CD8 antigen
14CD8-Positive T-Lymphocytes - immunology
15cell responses
16cells
17Clinical trials
18Cohort Studies
19Cross-Sectional Studies
20Cytokines
21Disease control
22ELISpot assay
23Enzyme-linked immunosorbent assay
24Enzyme-Linked Immunospot Assay
25Epidemiology
26Evaluation
27Flow Cytometry
28Health aspects
29HIV
30HIV (Viruses)
31HIV Infections - immunology
32HIV-1
33Human immunodeficiency virus
34Humans
35IFN-γ negative T-cells
36Immune response
37Immunogenicity
38Immunologic Factors - immunology
39Interferon
40Interferon gamma
41Interferon-gamma - immunology
42Interleukin 2
43Interleukin-2 - immunology
44Leukocytes (mononuclear)
45Leukocytes, Mononuclear - immunology
46Lymphocyte Activation
47Lymphocytes T
48Medical research
49Medicine, Experimental
50Peptides
51Peptides - immunology
52Perforin
53Perforin - immunology
54Peripheral blood mononuclear cells
55Phenotypes
56T cells
57T-cell responses
58Tumor Necrosis Factor-alpha - immunology
59Tumor necrosis factor-TNF
60Tumor necrosis factor-α
61Vaccines
62Viral antigens
63Viruses
64γ negative T
65γ-Interferon
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2Auma, Betty O
3Kintu, Christopher
4Lindan, Christina
5Nanteza, Mary Bridget
6Kaleebu, Pontiano
7Serwanga, Jennifer
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titleInterferon gamma (IFN-γ) negative CD4+ and CD8+ T-cells can produce immune mediators in response to viral antigens
authorNakiboneka, Ritah ; Mugaba, Susan ; Auma, Betty O ; Kintu, Christopher ; Lindan, Christina ; Nanteza, Mary Bridget ; Kaleebu, Pontiano ; Serwanga, Jennifer
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0Acquired immune deficiency syndrome
1Adenoviridae
2Adenoviruses
3AIDS
4Antigens
5Antigens, Viral - immunology
6Antiretroviral drugs
7Antiretroviral therapy
8Apoptosis
9Article
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20Cytokines
21Disease control
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24Enzyme-Linked Immunospot Assay
25Epidemiology
26Evaluation
27Flow Cytometry
28Health aspects
29HIV
30HIV (Viruses)
31HIV Infections - immunology
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33Human immunodeficiency virus
34Humans
35IFN-γ negative T-cells
36Immune response
37Immunogenicity
38Immunologic Factors - immunology
39Interferon
40Interferon gamma
41Interferon-gamma - immunology
42Interleukin 2
43Interleukin-2 - immunology
44Leukocytes (mononuclear)
45Leukocytes, Mononuclear - immunology
46Lymphocyte Activation
47Lymphocytes T
48Medical research
49Medicine, Experimental
50Peptides
51Peptides - immunology
52Perforin
53Perforin - immunology
54Peripheral blood mononuclear cells
55Phenotypes
56T cells
57T-cell responses
58Tumor Necrosis Factor-alpha - immunology
59Tumor necrosis factor-TNF
60Tumor necrosis factor-α
61Vaccines
62Viral antigens
63Viruses
64γ negative T
65γ-Interferon
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7Serwanga, Jennifer
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abstractEvaluation of antigen-specific T-cell responses to viral antigens is frequently performed on IFN-γ secreting cells. However, T-cells are capable of producing many more functions than just IFN-γ, some of which, like Perforin, are associated with immune protection in HIV-1 disease elite controllers. We evaluated the extent of missed T-cell functions when IFN-γ secretion is used as a surrogate marker for further evaluation of T-cell functions. Intracellular cytokine staining assay and flow cytometry were used to assess peripheral blood mononuclear cells (PBMCs) from 31 HIV-infected ART-naive individuals for the extent to which gated CD4+ and CD8+ IFN-γ producing and non-producing T-cells also secreted IL-2, Perforin, and TNF-α functions. Similarly, the extent of missed virus-specific responses in IFN-γ ELISpot assay negative T-cells from 5 HIV-1 uninfected individuals was evaluated. Cells from HIV-infected individuals were stimulated with pooled consensus group M (Con M) peptides; and those from healthy individuals were stimulated with pooled adenovirus (Ad) peptides. Overall, frequencies of virus-specific IFN-γ secreting CD4+ and CD8+ cells were low. Proportions of IFN-γ negative CD4+ expressing IL-2, Perforin, or TNF-α to Con M were significantly higher (5 of 7 functional profiles) than the corresponding IFN-γ positive CD4+ (0 of 7) T-cell phenotype, p = 0.02; Fisher’s Exact test. Likewise, proportions of CD8+ T-cells expressing other functions were significantly higher in 4 of the 7 IFN-γ negative CD8+ T-cells. Notably, newly stimulated Perforin, identified as Perforin co-expression with IL-2 or TNF-α, was significantly higher in IFN-γ negative CD8+ T-cell than in the positive CD8+ T-cells. Using SEB, lower responses in IFN-γ positive cells were most associated with CD4+ than CD8+ T-cells. These findings suggest that studies evaluating immunogenicity in response to HIV and Adenovirus viral antigens should not only evaluate T-cell responsiveness among IFN-γ producing cells but also among those T-cells that do not express IFN-γ.
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pubElsevier Ltd
pmid30459072
doi10.1016/j.vaccine.2018.11.024
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