Human Leukocyte Antigen-G and Regulatory T Cells During Specific Immunotherapy for Pollen Allergy

Louise Torp Dalgaard, Anja Elaine Sørensen, Claus Johnsen, Peter Würtzen, Bjarne Kristensen, Margit Larsen, Henrik Ullum, Ulrik Søes-Petersen, Thomas Hviid

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Background: TH2-biased immune responses are important in allergy pathogenesis. Mechanisms of allergen-specific immunotherapy (SIT) might include the induction of regulatory T cells (Tregs) and immunoglobulin (Ig) G4 blocking antibodies, a reduction in the number of effector cells, and skewing of the cytokine profile towards a TH1-polarized immune response. We investigated the effects of SIT on T cells, on immunomodulation of human leukocyte antigen (HLA)-G, which has been associated with allergy, on regulatory cytokine expression, and on serum allergen-specific antibody subclasses (IgE and IgG4). Methods: Eleven birch and/or grass pollen-allergic patients and 10 healthy nonatopic controls were studied before and during SIT. Tregs, chemokine receptors, soluble HLA-G (sHLA-G), Ig-like transcript (ILT) 2, specific IgE, and IgG4 were studied. Peripheral blood mononuclear cells (PBMCs) were stimulated with pollen extract in vitro and immune factors were evaluated. Results: During SIT, the main changes in the peripheral blood were an increase in CXCR3+CD4+CD25+CD127low/- Tregs and a decrease in CCR4+CD4+CD25+CD127low/- Tregs, an increase in allergen-specific IgG4, and a decrease in sHLA-G during the first half of the treatment period. In the PBMC in vitro experiments, the following changes were observed upon allergen-stimulation: an increase in CD4+CD25+CD127low/- Tregs and ILT2+CD4+CD25+CD127low/- Tregs, an increase in IL-10 and IL-2 levels, and an increase in sHLA-G that was most pronounced at the start of SIT. Conclusions: The changes in CXCR3+CD4+CD25+CD127low/- Treg, IgG4, and sHLA-G levels in the peripheral blood and in ILT2+ Treg, IL-10, IL-2, and sHLA-G levels upon in vitro allergen stimulation suggest an upregulation in immunomodulatory factors and, to some degree, a shift towards TH1 during SIT.
    Original languageEnglish
    JournalInternational Archives of Allergy and Immunology
    Volume162
    Issue number3
    Pages (from-to)237-252
    ISSN1018-2438
    DOIs
    Publication statusPublished - 6 Sep 2013

    Cite this

    Dalgaard, Louise Torp ; Sørensen, Anja Elaine ; Johnsen, Claus ; Würtzen, Peter ; Kristensen, Bjarne ; Larsen, Margit ; Ullum, Henrik ; Søes-Petersen, Ulrik ; Hviid, Thomas. / Human Leukocyte Antigen-G and Regulatory T Cells During Specific Immunotherapy for Pollen Allergy. In: International Archives of Allergy and Immunology. 2013 ; Vol. 162, No. 3. pp. 237-252.
    @article{1832fc13434e49219f58601443b30685,
    title = "Human Leukocyte Antigen-G and Regulatory T Cells During Specific Immunotherapy for Pollen Allergy",
    abstract = "Background: TH2-biased immune responses are important in allergy pathogenesis. Mechanisms of allergen-specific immunotherapy (SIT) might include the induction of regulatory T cells (Tregs) and immunoglobulin (Ig) G4 blocking antibodies, a reduction in the number of effector cells, and skewing of the cytokine profile towards a TH1-polarized immune response. We investigated the effects of SIT on T cells, on immunomodulation of human leukocyte antigen (HLA)-G, which has been associated with allergy, on regulatory cytokine expression, and on serum allergen-specific antibody subclasses (IgE and IgG4). Methods: Eleven birch and/or grass pollen-allergic patients and 10 healthy nonatopic controls were studied before and during SIT. Tregs, chemokine receptors, soluble HLA-G (sHLA-G), Ig-like transcript (ILT) 2, specific IgE, and IgG4 were studied. Peripheral blood mononuclear cells (PBMCs) were stimulated with pollen extract in vitro and immune factors were evaluated. Results: During SIT, the main changes in the peripheral blood were an increase in CXCR3+CD4+CD25+CD127low/- Tregs and a decrease in CCR4+CD4+CD25+CD127low/- Tregs, an increase in allergen-specific IgG4, and a decrease in sHLA-G during the first half of the treatment period. In the PBMC in vitro experiments, the following changes were observed upon allergen-stimulation: an increase in CD4+CD25+CD127low/- Tregs and ILT2+CD4+CD25+CD127low/- Tregs, an increase in IL-10 and IL-2 levels, and an increase in sHLA-G that was most pronounced at the start of SIT. Conclusions: The changes in CXCR3+CD4+CD25+CD127low/- Treg, IgG4, and sHLA-G levels in the peripheral blood and in ILT2+ Treg, IL-10, IL-2, and sHLA-G levels upon in vitro allergen stimulation suggest an upregulation in immunomodulatory factors and, to some degree, a shift towards TH1 during SIT.",
    author = "Dalgaard, {Louise Torp} and S{\o}rensen, {Anja Elaine} and Claus Johnsen and Peter W{\"u}rtzen and Bjarne Kristensen and Margit Larsen and Henrik Ullum and Ulrik S{\o}es-Petersen and Thomas Hviid",
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    Human Leukocyte Antigen-G and Regulatory T Cells During Specific Immunotherapy for Pollen Allergy. / Dalgaard, Louise Torp; Sørensen, Anja Elaine; Johnsen, Claus; Würtzen, Peter; Kristensen, Bjarne; Larsen, Margit; Ullum, Henrik; Søes-Petersen, Ulrik; Hviid, Thomas.

    In: International Archives of Allergy and Immunology, Vol. 162, No. 3, 06.09.2013, p. 237-252.

    Research output: Contribution to journalJournal articleResearchpeer-review

    TY - JOUR

    T1 - Human Leukocyte Antigen-G and Regulatory T Cells During Specific Immunotherapy for Pollen Allergy

    AU - Dalgaard, Louise Torp

    AU - Sørensen, Anja Elaine

    AU - Johnsen, Claus

    AU - Würtzen, Peter

    AU - Kristensen, Bjarne

    AU - Larsen, Margit

    AU - Ullum, Henrik

    AU - Søes-Petersen, Ulrik

    AU - Hviid, Thomas

    PY - 2013/9/6

    Y1 - 2013/9/6

    N2 - Background: TH2-biased immune responses are important in allergy pathogenesis. Mechanisms of allergen-specific immunotherapy (SIT) might include the induction of regulatory T cells (Tregs) and immunoglobulin (Ig) G4 blocking antibodies, a reduction in the number of effector cells, and skewing of the cytokine profile towards a TH1-polarized immune response. We investigated the effects of SIT on T cells, on immunomodulation of human leukocyte antigen (HLA)-G, which has been associated with allergy, on regulatory cytokine expression, and on serum allergen-specific antibody subclasses (IgE and IgG4). Methods: Eleven birch and/or grass pollen-allergic patients and 10 healthy nonatopic controls were studied before and during SIT. Tregs, chemokine receptors, soluble HLA-G (sHLA-G), Ig-like transcript (ILT) 2, specific IgE, and IgG4 were studied. Peripheral blood mononuclear cells (PBMCs) were stimulated with pollen extract in vitro and immune factors were evaluated. Results: During SIT, the main changes in the peripheral blood were an increase in CXCR3+CD4+CD25+CD127low/- Tregs and a decrease in CCR4+CD4+CD25+CD127low/- Tregs, an increase in allergen-specific IgG4, and a decrease in sHLA-G during the first half of the treatment period. In the PBMC in vitro experiments, the following changes were observed upon allergen-stimulation: an increase in CD4+CD25+CD127low/- Tregs and ILT2+CD4+CD25+CD127low/- Tregs, an increase in IL-10 and IL-2 levels, and an increase in sHLA-G that was most pronounced at the start of SIT. Conclusions: The changes in CXCR3+CD4+CD25+CD127low/- Treg, IgG4, and sHLA-G levels in the peripheral blood and in ILT2+ Treg, IL-10, IL-2, and sHLA-G levels upon in vitro allergen stimulation suggest an upregulation in immunomodulatory factors and, to some degree, a shift towards TH1 during SIT.

    AB - Background: TH2-biased immune responses are important in allergy pathogenesis. Mechanisms of allergen-specific immunotherapy (SIT) might include the induction of regulatory T cells (Tregs) and immunoglobulin (Ig) G4 blocking antibodies, a reduction in the number of effector cells, and skewing of the cytokine profile towards a TH1-polarized immune response. We investigated the effects of SIT on T cells, on immunomodulation of human leukocyte antigen (HLA)-G, which has been associated with allergy, on regulatory cytokine expression, and on serum allergen-specific antibody subclasses (IgE and IgG4). Methods: Eleven birch and/or grass pollen-allergic patients and 10 healthy nonatopic controls were studied before and during SIT. Tregs, chemokine receptors, soluble HLA-G (sHLA-G), Ig-like transcript (ILT) 2, specific IgE, and IgG4 were studied. Peripheral blood mononuclear cells (PBMCs) were stimulated with pollen extract in vitro and immune factors were evaluated. Results: During SIT, the main changes in the peripheral blood were an increase in CXCR3+CD4+CD25+CD127low/- Tregs and a decrease in CCR4+CD4+CD25+CD127low/- Tregs, an increase in allergen-specific IgG4, and a decrease in sHLA-G during the first half of the treatment period. In the PBMC in vitro experiments, the following changes were observed upon allergen-stimulation: an increase in CD4+CD25+CD127low/- Tregs and ILT2+CD4+CD25+CD127low/- Tregs, an increase in IL-10 and IL-2 levels, and an increase in sHLA-G that was most pronounced at the start of SIT. Conclusions: The changes in CXCR3+CD4+CD25+CD127low/- Treg, IgG4, and sHLA-G levels in the peripheral blood and in ILT2+ Treg, IL-10, IL-2, and sHLA-G levels upon in vitro allergen stimulation suggest an upregulation in immunomodulatory factors and, to some degree, a shift towards TH1 during SIT.

    U2 - 10.1159/000353281

    DO - 10.1159/000353281

    M3 - Journal article

    VL - 162

    SP - 237

    EP - 252

    JO - International Archives of Allergy and Immunology

    JF - International Archives of Allergy and Immunology

    SN - 1018-2438

    IS - 3

    ER -