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

Anja Elaine Sørensen; Claus R Johnsen; Louise Torp Dalgaard; Peter Adler Würtzen; Bjarne Kristensen; Margit Hørup Larsen; Henrik Ullum; Ulrik Søes-Petersen; Thomas Vauvert F Hviid

doi:10.1159/000353281

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

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

Department of Clinical Medicine

5 Citations (Scopus)

Abstract

Background: T_H2-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 T_H1-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⁺CD127^low/- Tregs and a decrease in CCR4⁺CD4⁺CD25⁺CD127^low/- 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⁺CD127^low/- Tregs and ILT2⁺CD4⁺CD25⁺CD127^low/- 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⁺CD127^low/- 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 T_H1 during SIT.

Original language	English
Journal	International Archives of Allergy and Immunology
Volume	162
Issue number	3
Pages (from-to)	237-252
Number of pages	16
ISSN	1018-2438
DOIs	https://doi.org/10.1159/000353281
Publication status	Published - 2013

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@article{b4519b71b51b4cd09f654cfe7b63912e,

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 = "S{\o}rensen, {Anja Elaine} and Johnsen, {Claus R} and Dalgaard, {Louise Torp} and W{\"u}rtzen, {Peter Adler} and Bjarne Kristensen and Larsen, {Margit H{\o}rup} and Henrik Ullum and Ulrik S{\o}es-Petersen and Hviid, {Thomas Vauvert F}",

year = "2013",

doi = "10.1159/000353281",

language = "English",

volume = "162",

pages = "237--252",

journal = "International Archives of Allergy and Immunology",

issn = "1018-2438",

publisher = "S Karger AG",

number = "3",

}

TY - JOUR

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

AU - Sørensen, Anja Elaine

AU - Johnsen, Claus R

AU - Dalgaard, Louise Torp

AU - Würtzen, Peter Adler

AU - Kristensen, Bjarne

AU - Larsen, Margit Hørup

AU - Ullum, Henrik

AU - Søes-Petersen, Ulrik

AU - Hviid, Thomas Vauvert F

PY - 2013

Y1 - 2013

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

C2 - 24022071

SN - 1018-2438

VL - 162

SP - 237

EP - 252

JO - International Archives of Allergy and Immunology

JF - International Archives of Allergy and Immunology

IS - 3

ER -

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

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