Increasing the ex vivo antigen-specific IFN-γ production in subpopulations of T cells and NKp46+ cells by anti-CD28, anti-CD49d and recombinant IL-12 costimulation in cattle vaccinated with recombinant proteins from Mycobacterium avium subspecies paratuberculosis

Aneesh Thakur; Ulla Riber; William C Davis; Gregers Jungersen

doi:10.1016/j.vetimm.2013.08.009

Increasing the ex vivo antigen-specific IFN-γ production in subpopulations of T cells and NKp46+ cells by anti-CD28, anti-CD49d and recombinant IL-12 costimulation in cattle vaccinated with recombinant proteins from Mycobacterium avium subspecies paratuberculosis

Aneesh Thakur, Ulla Riber, William C Davis, Gregers Jungersen

4 Citations (Scopus)

Abstract

T cells, which encounter specific antigen (Ag), require additional signals to mount a functional immune response. Here, we demonstrate activation of signal 2, by anti-CD28 mAb (aCD28) and other costimulatory molecules (aCD49d, aCD5), and signal 3, by recombinant IL-12, enhance Ag-specific IFN-γ secretion by CD4, CD8, γδ T cells and NK cells. Age matched male jersey calves, experimentally infected with Mycobacterium avium subsp. paratuberculosis (MAP), were vaccinated with a cocktail of recombinant MAP proteins or left unvaccinated. Vaccine induced ex vivo recall responses were measured through Ag-specific IFN-γ production by ELISA and flow cytometry. There was a significant increase in production of IFN-γ by T cell subsets or NKp46+ cells cultured in the presence of Ag and aCD28/aCD49d. The increase was accompanied by an increase in the integrated median fluorescence intensity (iMFI) of activated T cells. Addition of rIL-12 induced a significant additive effect leading to a maximum increase in responder frequency of Ag-specific T cell subsets or NKp46+ cells with a heavy bias toward IFN-γ production by CD4 T cells. We provide the first description of using aCD28/aCD49d costimulation to potentiate an Ag-specific increase in the production of IFN-γ in bovine immunology. The study also shows the degree of signaling in T cells is regulated by the costimulatory environment.

Original language	English
Journal	Veterinary Immunology and Immunopathology
Volume	155
Issue number	4
Pages (from-to)	276-83
Number of pages	8
ISSN	0165-2427
DOIs	https://doi.org/10.1016/j.vetimm.2013.08.009
Publication status	Published - 1 Oct 2013

Keywords

Animals
Antibodies, Bacterial/analysis
Antibodies, Monoclonal/pharmacology
CD4-Positive T-Lymphocytes/immunology
Cattle
Cattle Diseases/blood
Enzyme-Linked Immunosorbent Assay/veterinary
Flow Cytometry/veterinary
Interferon-gamma/analysis
Leukocytes, Mononuclear
Male
Mycobacterium avium subsp. paratuberculosis/immunology
Paratuberculosis/immunology
Signal Transduction/immunology
Statistics, Nonparametric
Vaccination/veterinary

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Thakur, A., Riber, U., Davis, W. C., & Jungersen, G. (2013). Increasing the ex vivo antigen-specific IFN-γ production in subpopulations of T cells and NKp46+ cells by anti-CD28, anti-CD49d and recombinant IL-12 costimulation in cattle vaccinated with recombinant proteins from Mycobacterium avium subspecies paratuberculosis. Veterinary Immunology and Immunopathology, 155(4), 276-83. https://doi.org/10.1016/j.vetimm.2013.08.009

Increasing the ex vivo antigen-specific IFN-γ production in subpopulations of T cells and NKp46+ cells by anti-CD28, anti-CD49d and recombinant IL-12 costimulation in cattle vaccinated with recombinant proteins from Mycobacterium avium subspecies paratuberculosis. / Thakur, Aneesh; Riber, Ulla; Davis, William C et al.
In: Veterinary Immunology and Immunopathology, Vol. 155, No. 4, 01.10.2013, p. 276-83.

Research output: Contribution to journal › Journal article › Research › peer-review

Thakur, A, Riber, U, Davis, WC & Jungersen, G 2013, 'Increasing the ex vivo antigen-specific IFN-γ production in subpopulations of T cells and NKp46+ cells by anti-CD28, anti-CD49d and recombinant IL-12 costimulation in cattle vaccinated with recombinant proteins from Mycobacterium avium subspecies paratuberculosis', Veterinary Immunology and Immunopathology, vol. 155, no. 4, pp. 276-83. https://doi.org/10.1016/j.vetimm.2013.08.009

Thakur A, Riber U, Davis WC, Jungersen G. Increasing the ex vivo antigen-specific IFN-γ production in subpopulations of T cells and NKp46+ cells by anti-CD28, anti-CD49d and recombinant IL-12 costimulation in cattle vaccinated with recombinant proteins from Mycobacterium avium subspecies paratuberculosis. Veterinary Immunology and Immunopathology. 2013 Oct 1;155(4):276-83. doi: 10.1016/j.vetimm.2013.08.009

Thakur, Aneesh ; Riber, Ulla ; Davis, William C et al. / Increasing the ex vivo antigen-specific IFN-γ production in subpopulations of T cells and NKp46+ cells by anti-CD28, anti-CD49d and recombinant IL-12 costimulation in cattle vaccinated with recombinant proteins from Mycobacterium avium subspecies paratuberculosis. In: Veterinary Immunology and Immunopathology. 2013 ; Vol. 155, No. 4. pp. 276-83.

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abstract = "T cells, which encounter specific antigen (Ag), require additional signals to mount a functional immune response. Here, we demonstrate activation of signal 2, by anti-CD28 mAb (aCD28) and other costimulatory molecules (aCD49d, aCD5), and signal 3, by recombinant IL-12, enhance Ag-specific IFN-γ secretion by CD4, CD8, γδ T cells and NK cells. Age matched male jersey calves, experimentally infected with Mycobacterium avium subsp. paratuberculosis (MAP), were vaccinated with a cocktail of recombinant MAP proteins or left unvaccinated. Vaccine induced ex vivo recall responses were measured through Ag-specific IFN-γ production by ELISA and flow cytometry. There was a significant increase in production of IFN-γ by T cell subsets or NKp46+ cells cultured in the presence of Ag and aCD28/aCD49d. The increase was accompanied by an increase in the integrated median fluorescence intensity (iMFI) of activated T cells. Addition of rIL-12 induced a significant additive effect leading to a maximum increase in responder frequency of Ag-specific T cell subsets or NKp46+ cells with a heavy bias toward IFN-γ production by CD4 T cells. We provide the first description of using aCD28/aCD49d costimulation to potentiate an Ag-specific increase in the production of IFN-γ in bovine immunology. The study also shows the degree of signaling in T cells is regulated by the costimulatory environment. ",

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author = "Aneesh Thakur and Ulla Riber and Davis, {William C} and Gregers Jungersen",

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T1 - Increasing the ex vivo antigen-specific IFN-γ production in subpopulations of T cells and NKp46+ cells by anti-CD28, anti-CD49d and recombinant IL-12 costimulation in cattle vaccinated with recombinant proteins from Mycobacterium avium subspecies paratuberculosis

AU - Thakur, Aneesh

AU - Riber, Ulla

AU - Davis, William C

AU - Jungersen, Gregers

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N2 - T cells, which encounter specific antigen (Ag), require additional signals to mount a functional immune response. Here, we demonstrate activation of signal 2, by anti-CD28 mAb (aCD28) and other costimulatory molecules (aCD49d, aCD5), and signal 3, by recombinant IL-12, enhance Ag-specific IFN-γ secretion by CD4, CD8, γδ T cells and NK cells. Age matched male jersey calves, experimentally infected with Mycobacterium avium subsp. paratuberculosis (MAP), were vaccinated with a cocktail of recombinant MAP proteins or left unvaccinated. Vaccine induced ex vivo recall responses were measured through Ag-specific IFN-γ production by ELISA and flow cytometry. There was a significant increase in production of IFN-γ by T cell subsets or NKp46+ cells cultured in the presence of Ag and aCD28/aCD49d. The increase was accompanied by an increase in the integrated median fluorescence intensity (iMFI) of activated T cells. Addition of rIL-12 induced a significant additive effect leading to a maximum increase in responder frequency of Ag-specific T cell subsets or NKp46+ cells with a heavy bias toward IFN-γ production by CD4 T cells. We provide the first description of using aCD28/aCD49d costimulation to potentiate an Ag-specific increase in the production of IFN-γ in bovine immunology. The study also shows the degree of signaling in T cells is regulated by the costimulatory environment.

AB - T cells, which encounter specific antigen (Ag), require additional signals to mount a functional immune response. Here, we demonstrate activation of signal 2, by anti-CD28 mAb (aCD28) and other costimulatory molecules (aCD49d, aCD5), and signal 3, by recombinant IL-12, enhance Ag-specific IFN-γ secretion by CD4, CD8, γδ T cells and NK cells. Age matched male jersey calves, experimentally infected with Mycobacterium avium subsp. paratuberculosis (MAP), were vaccinated with a cocktail of recombinant MAP proteins or left unvaccinated. Vaccine induced ex vivo recall responses were measured through Ag-specific IFN-γ production by ELISA and flow cytometry. There was a significant increase in production of IFN-γ by T cell subsets or NKp46+ cells cultured in the presence of Ag and aCD28/aCD49d. The increase was accompanied by an increase in the integrated median fluorescence intensity (iMFI) of activated T cells. Addition of rIL-12 induced a significant additive effect leading to a maximum increase in responder frequency of Ag-specific T cell subsets or NKp46+ cells with a heavy bias toward IFN-γ production by CD4 T cells. We provide the first description of using aCD28/aCD49d costimulation to potentiate an Ag-specific increase in the production of IFN-γ in bovine immunology. The study also shows the degree of signaling in T cells is regulated by the costimulatory environment.

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KW - Antibodies, Bacterial/analysis

KW - Antibodies, Monoclonal/pharmacology

KW - CD4-Positive T-Lymphocytes/immunology

KW - Cattle

KW - Cattle Diseases/blood

KW - Enzyme-Linked Immunosorbent Assay/veterinary

KW - Flow Cytometry/veterinary

KW - Interferon-gamma/analysis

KW - Leukocytes, Mononuclear

KW - Male

KW - Mycobacterium avium subsp. paratuberculosis/immunology

KW - Paratuberculosis/immunology

KW - Signal Transduction/immunology

KW - Statistics, Nonparametric

KW - Vaccination/veterinary

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DO - 10.1016/j.vetimm.2013.08.009

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C2 - 24034934

SN - 0165-2427

VL - 155

SP - 276

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JO - Veterinary Immunology and Immunopathology

JF - Veterinary Immunology and Immunopathology

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