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(+)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 TH1 during SIT.
authors.affiliation: Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), Copenhagen University Hospital (Roskilde) and Roskilde Hospital, Roskilde, Denmark.
authors.forename: Anja E
authors.initials: AE
authors.lastname: Sørensen
authors.forename: Claus R
authors.initials: CR
authors.lastname: Johnsen
authors.forename: Louise T
authors.initials: LT
authors.lastname: Dalgaard
authors.forename: Peter Adler
authors.initials: PA
authors.lastname: Würtzen
authors.forename: Bjarne
authors.initials: B
authors.lastname: Kristensen
authors.forename: Margit Hørup
authors.initials: MH
authors.lastname: Larsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Ullum
authors.forename: Ulrik
authors.initials: U
authors.lastname: Søes-Petersen
authors.forename: Thomas Vauvert F
authors.initials: TV
authors.lastname: Hviid
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005260:Female; D059951:HLA-G Antigens / Q000097:blood / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016130:Immunophenotyping; D007167:Immunotherapy; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011058:Pollen / Q000276:immunology*; D054398:Receptors, CCR4 / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000485:Allergens; D016207:Cytokines; D018985:Epitopes, B-Lymphocyte; D059951:HLA-G Antigens; D007074:Immunoglobulin G; D054398:Receptors, CCR4; D054367:Receptors, CXCR3