Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), Copenhagen University Hospital (Roskilde) and Roskilde Hospital, Roskilde, Denmark.
Int Arch Allergy Immunol. 2013;162(3):237-52. doi: 10.1159/000353281. Epub 2013 Sep 6.
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).
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.
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.
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.
TH2 偏向性免疫应答在过敏发病机制中很重要。变应原特异性免疫疗法（SIT）的机制可能包括诱导调节性 T 细胞（Tregs）和免疫球蛋白（Ig）G4 阻断抗体，减少效应细胞数量，以及使细胞因子谱向 TH1 极化免疫反应倾斜。我们研究了 SIT 对 T 细胞的影响，对与过敏相关的人类白细胞抗原（HLA）-G 的免疫调节作用，对调节性细胞因子表达的影响，以及对血清变应原特异性抗体亚类（IgE 和 IgG4）的影响。
研究了 11 名桦树和/或草花粉过敏患者和 10 名健康非过敏对照者在 SIT 前后的 T 细胞、免疫调节 HLA-G、调节性细胞因子表达和血清变应原特异性抗体亚类（IgE 和 IgG4）。用花粉提取物体外刺激外周血单核细胞（PBMCs），并评估免疫因子。
在 SIT 期间，外周血中的主要变化是 CXCR3(+)CD4(+)CD25(+)CD127(low/-)Tregs 增加，CCR4(+)CD4(+)CD25(+)CD127(low/-)Tregs 减少，过敏原特异性 IgG4 增加，以及治疗前半段 sHLA-G 减少。在 PBMC 体外实验中，在变应原刺激下观察到以下变化：CD4(+)CD25(+)CD127(low/-)Tregs 和 ILT2(+)CD4(+)CD25(+)CD127(low/-)Tregs 增加，IL-10 和 IL-2 水平增加，sHLA-G 增加，SIT 开始时最为明显。
外周血中 CXCR3(+)CD4(+)CD25(+)CD127(low/-)Treg、IgG4 和 sHLA-G 水平以及体外过敏原刺激下 ILT2(+)Treg、IL-10、IL-2 和 sHLA-G 水平的变化表明，免疫调节因子的上调，在某种程度上，SIT 期间向 TH1 倾斜。
