An adjuvant formulation that preferentially induces T helper cell type 1 cytokine and CD8+ cytotoxic responses is associated with up-regulation of IL-12 and suppression of IL-10 production

J. M. Brewer, C. W. Roberts, M. Conacher, J. McColl, B. A. Blarney, J. Alexander

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Adjuvant preparations of Non-ionic surfactant vesicles (NISV) were compared, where appropriate, with Alum and Freund's complete adjuvant (FCA) for their ability to stimulate humoral and classical cell-mediated immune responses to a standard antigen, ovalbumin (OVA), and cell-mediated responses to a known T-cell epitope in BALB/c mice. Although NISV were able to induce antigen-specific, interferon-γ (IFN-γ) dependent, immunoglobulin G2a (IgG2a) production, the antibody response using Alum as adjuvant consisted entirely of the IgG1 isotype. Although OVA-specific lymphocyte proliferation in vitro was similarly enhanced by the use of Alum or NISV as adjuvant, cytokines detected in the culture supernatants were markedly different. Whereas production of the T helper cell 2 (Th2)-associated cytokine, interleukin-5 (IL-5), was significantly enhanced when Alum was used, the Th1-associated cytokine, IL-2, was primarily produced when NISVs were used as adjuvants. The use of this adjuvant also enhanced cytotoxic T-cell responses to OVA. Significant T-cell proliferation could also be generated against a synthetic peptide containing a T-cell epitope derived from the amino acid sequence of measles fusion protein when NISVs were used as adjuvant, but not FCA (Freund's Complete Adjuvant). In fact, over a range of antigen concentrations, greater stimulation indices were produced using NISV rather than FCA as adjuvant. Similarly, greater (though not significantly greater) quantities of the Th1-associated cytokine IFN-γ, were produced by antigen-stimulated lymphocytes when NISVs were used compared with FCA as adjuvant. Ex vivo studies of IL-12 and IL-10 production indicated that following administration of NISV, splenocytes were primed for increased IL-12 production, whereas IL-10 production was down regulated. We conclude that NISVs are effective adjuvants capable of stimulating Th1 and cytotoxic T-cell responses against protein and synthetic peptide antigens. Our results also suggest that this activity is associated with the ability of NISV to modulate IL-10 and IL-12 production to favor generation of Th1-type immune responses.

LanguageEnglish
Pages77-89
Number of pages13
JournalVaccine Research
Volume5
Issue number2
Publication statusPublished - 1 Jan 1996

Fingerprint

Th1 Cells
Interleukin-12
Surface-Active Agents
Interleukin-10
Up-Regulation
Freund's Adjuvant
Cytokines
Ovalbumin
Antigens
T-Lymphocyte Epitopes
T-Lymphocytes
Interferon-gamma
Viral Fusion Proteins
Lymphocytes
Th2 Cells
Peptides
Synthetic Vaccines
Interleukin-5
Antibody Formation
Interleukin-2

Keywords

  • aluminum potassium sulfate
  • cd8 antigen
  • cytokine
  • freund adjuvant
  • gamma interferon
  • immunoglobulin g1
  • immunoglobulin g2a

Cite this

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title = "An adjuvant formulation that preferentially induces T helper cell type 1 cytokine and CD8+ cytotoxic responses is associated with up-regulation of IL-12 and suppression of IL-10 production",
abstract = "Adjuvant preparations of Non-ionic surfactant vesicles (NISV) were compared, where appropriate, with Alum and Freund's complete adjuvant (FCA) for their ability to stimulate humoral and classical cell-mediated immune responses to a standard antigen, ovalbumin (OVA), and cell-mediated responses to a known T-cell epitope in BALB/c mice. Although NISV were able to induce antigen-specific, interferon-γ (IFN-γ) dependent, immunoglobulin G2a (IgG2a) production, the antibody response using Alum as adjuvant consisted entirely of the IgG1 isotype. Although OVA-specific lymphocyte proliferation in vitro was similarly enhanced by the use of Alum or NISV as adjuvant, cytokines detected in the culture supernatants were markedly different. Whereas production of the T helper cell 2 (Th2)-associated cytokine, interleukin-5 (IL-5), was significantly enhanced when Alum was used, the Th1-associated cytokine, IL-2, was primarily produced when NISVs were used as adjuvants. The use of this adjuvant also enhanced cytotoxic T-cell responses to OVA. Significant T-cell proliferation could also be generated against a synthetic peptide containing a T-cell epitope derived from the amino acid sequence of measles fusion protein when NISVs were used as adjuvant, but not FCA (Freund's Complete Adjuvant). In fact, over a range of antigen concentrations, greater stimulation indices were produced using NISV rather than FCA as adjuvant. Similarly, greater (though not significantly greater) quantities of the Th1-associated cytokine IFN-γ, were produced by antigen-stimulated lymphocytes when NISVs were used compared with FCA as adjuvant. Ex vivo studies of IL-12 and IL-10 production indicated that following administration of NISV, splenocytes were primed for increased IL-12 production, whereas IL-10 production was down regulated. We conclude that NISVs are effective adjuvants capable of stimulating Th1 and cytotoxic T-cell responses against protein and synthetic peptide antigens. Our results also suggest that this activity is associated with the ability of NISV to modulate IL-10 and IL-12 production to favor generation of Th1-type immune responses.",
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author = "Brewer, {J. M.} and Roberts, {C. W.} and M. Conacher and J. McColl and Blarney, {B. A.} and J. Alexander",
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An adjuvant formulation that preferentially induces T helper cell type 1 cytokine and CD8+ cytotoxic responses is associated with up-regulation of IL-12 and suppression of IL-10 production. / Brewer, J. M.; Roberts, C. W.; Conacher, M.; McColl, J.; Blarney, B. A.; Alexander, J.

Vol. 5, No. 2, 01.01.1996, p. 77-89.

Research output: Contribution to journalArticle

TY - JOUR

T1 - An adjuvant formulation that preferentially induces T helper cell type 1 cytokine and CD8+ cytotoxic responses is associated with up-regulation of IL-12 and suppression of IL-10 production

AU - Brewer, J. M.

AU - Roberts, C. W.

AU - Conacher, M.

AU - McColl, J.

AU - Blarney, B. A.

AU - Alexander, J.

PY - 1996/1/1

Y1 - 1996/1/1

N2 - Adjuvant preparations of Non-ionic surfactant vesicles (NISV) were compared, where appropriate, with Alum and Freund's complete adjuvant (FCA) for their ability to stimulate humoral and classical cell-mediated immune responses to a standard antigen, ovalbumin (OVA), and cell-mediated responses to a known T-cell epitope in BALB/c mice. Although NISV were able to induce antigen-specific, interferon-γ (IFN-γ) dependent, immunoglobulin G2a (IgG2a) production, the antibody response using Alum as adjuvant consisted entirely of the IgG1 isotype. Although OVA-specific lymphocyte proliferation in vitro was similarly enhanced by the use of Alum or NISV as adjuvant, cytokines detected in the culture supernatants were markedly different. Whereas production of the T helper cell 2 (Th2)-associated cytokine, interleukin-5 (IL-5), was significantly enhanced when Alum was used, the Th1-associated cytokine, IL-2, was primarily produced when NISVs were used as adjuvants. The use of this adjuvant also enhanced cytotoxic T-cell responses to OVA. Significant T-cell proliferation could also be generated against a synthetic peptide containing a T-cell epitope derived from the amino acid sequence of measles fusion protein when NISVs were used as adjuvant, but not FCA (Freund's Complete Adjuvant). In fact, over a range of antigen concentrations, greater stimulation indices were produced using NISV rather than FCA as adjuvant. Similarly, greater (though not significantly greater) quantities of the Th1-associated cytokine IFN-γ, were produced by antigen-stimulated lymphocytes when NISVs were used compared with FCA as adjuvant. Ex vivo studies of IL-12 and IL-10 production indicated that following administration of NISV, splenocytes were primed for increased IL-12 production, whereas IL-10 production was down regulated. We conclude that NISVs are effective adjuvants capable of stimulating Th1 and cytotoxic T-cell responses against protein and synthetic peptide antigens. Our results also suggest that this activity is associated with the ability of NISV to modulate IL-10 and IL-12 production to favor generation of Th1-type immune responses.

AB - Adjuvant preparations of Non-ionic surfactant vesicles (NISV) were compared, where appropriate, with Alum and Freund's complete adjuvant (FCA) for their ability to stimulate humoral and classical cell-mediated immune responses to a standard antigen, ovalbumin (OVA), and cell-mediated responses to a known T-cell epitope in BALB/c mice. Although NISV were able to induce antigen-specific, interferon-γ (IFN-γ) dependent, immunoglobulin G2a (IgG2a) production, the antibody response using Alum as adjuvant consisted entirely of the IgG1 isotype. Although OVA-specific lymphocyte proliferation in vitro was similarly enhanced by the use of Alum or NISV as adjuvant, cytokines detected in the culture supernatants were markedly different. Whereas production of the T helper cell 2 (Th2)-associated cytokine, interleukin-5 (IL-5), was significantly enhanced when Alum was used, the Th1-associated cytokine, IL-2, was primarily produced when NISVs were used as adjuvants. The use of this adjuvant also enhanced cytotoxic T-cell responses to OVA. Significant T-cell proliferation could also be generated against a synthetic peptide containing a T-cell epitope derived from the amino acid sequence of measles fusion protein when NISVs were used as adjuvant, but not FCA (Freund's Complete Adjuvant). In fact, over a range of antigen concentrations, greater stimulation indices were produced using NISV rather than FCA as adjuvant. Similarly, greater (though not significantly greater) quantities of the Th1-associated cytokine IFN-γ, were produced by antigen-stimulated lymphocytes when NISVs were used compared with FCA as adjuvant. Ex vivo studies of IL-12 and IL-10 production indicated that following administration of NISV, splenocytes were primed for increased IL-12 production, whereas IL-10 production was down regulated. We conclude that NISVs are effective adjuvants capable of stimulating Th1 and cytotoxic T-cell responses against protein and synthetic peptide antigens. Our results also suggest that this activity is associated with the ability of NISV to modulate IL-10 and IL-12 production to favor generation of Th1-type immune responses.

KW - aluminum potassium sulfate

KW - cd8 antigen

KW - cytokine

KW - freund adjuvant

KW - gamma interferon

KW - immunoglobulin g1

KW - immunoglobulin g2a

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M3 - Article

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