PMID- 24022071 OWN - NLM STAT- MEDLINE DCOM- 20131219 LR - 20131025 IS - 1423-0097 (Electronic) IS - 1018-2438 (Linking) VI - 162 IP - 3 DP - 2013 TI - Human leukocyte antigen-G and regulatory T cells during specific immunotherapy for pollen allergy. PG - 237-52 LID - 10.1159/000353281 [doi] 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(+)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. CI - Copyright (c) 2013 S. Karger AG, Basel. FAU - Sorensen, Anja E AU - Sorensen AE AD - Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), Copenhagen University Hospital (Roskilde) and Roskilde Hospital, Roskilde, Denmark. FAU - Johnsen, Claus R AU - Johnsen CR FAU - Dalgaard, Louise T AU - Dalgaard LT FAU - Wurtzen, Peter Adler AU - Wurtzen PA FAU - Kristensen, Bjarne AU - Kristensen B FAU - Larsen, Margit Horup AU - Larsen MH FAU - Ullum, Henrik AU - Ullum H FAU - Soes-Petersen, Ulrik AU - Soes-Petersen U FAU - Hviid, Thomas Vauvert F AU - Hviid TV LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130906 PL - Switzerland TA - Int Arch Allergy Immunol JT - International archives of allergy and immunology JID - 9211652 RN - 0 (Allergens) RN - 0 (Cytokines) RN - 0 (Epitopes, B-Lymphocyte) RN - 0 (HLA-G Antigens) RN - 0 (Immunoglobulin G) RN - 0 (Receptors, CCR4) RN - 0 (Receptors, CXCR3) SB - IM MH - Adult MH - Allergens/*immunology MH - Cytokines/biosynthesis MH - Epitopes, B-Lymphocyte/immunology MH - Female MH - HLA-G Antigens/blood/*immunology MH - Humans MH - Immunoglobulin G/blood/immunology MH - Immunophenotyping MH - *Immunotherapy MH - Leukocytes, Mononuclear/immunology/metabolism MH - Male MH - Middle Aged MH - Pollen/*immunology MH - Receptors, CCR4/metabolism MH - Receptors, CXCR3/metabolism MH - Rhinitis, Allergic, Seasonal/*immunology/*therapy MH - T-Lymphocytes, Regulatory/*immunology/metabolism MH - Young Adult EDAT- 2013/09/12 06:00 MHDA- 2013/12/20 06:00 CRDT- 2013/09/12 06:00 PHST- 2012/11/28 00:00 [received] PHST- 2013/05/24 00:00 [accepted] PHST- 2013/09/12 06:00 [entrez] PHST- 2013/09/12 06:00 [pubmed] PHST- 2013/12/20 06:00 [medline] AID - 000353281 [pii] AID - 10.1159/000353281 [doi] PST - ppublish SO - Int Arch Allergy Immunol. 2013;162(3):237-52. doi: 10.1159/000353281. Epub 2013 Sep 6.