T 细胞对主要草过敏原的反应受到调节,包括在特应性而非非特应性受试者中产生 IL-10。
The T cell response to major grass allergens is regulated and includes IL-10 production in atopic but not in non-atopic subjects.
机构信息
Department of Experimental Immunology, ALK-Abelló, Hoersholm, Denmark.
出版信息
Int Arch Allergy Immunol. 2010;152(3):243-54. doi: 10.1159/000283033. Epub 2010 Feb 11.
BACKGROUND
The incidence of allergic diseases is increasing in industrialized countries and the immunological mechanisms leading to tolerance or allergy are poorly understood. Cytokines with suppressive abilities and CD4(+)CD25(+) regulatory T cells have been suggested to play a central role in allergen-specific responses. The aim was to determine whether major grass allergens induce production of suppressive cytokines in allergic and healthy subjects and to examine the inhibitory effect of these cytokines on allergic responses.
METHODS
Peripheral blood mononuclear cells (PBMCs) were isolated from healthy and grass-allergic donors and stimulated with the major grass allergens Phl p 1 or Phl p 5. The effects of endogenous IL-10 and/or TGF-beta on proliferation and cytokine production were determined by use of blocking antibodies. In addition, the number of CD4(+)CD25(+) T cells and their expression of chemokine receptors were investigated by flow cytometry.
RESULTS
Phl p 1 and Phl p 5 induced IL-10 production, which down-regulated proliferation and cytokine production, in PBMC cultures from atopic but not from non-atopic donors. Comparable frequencies of CD4(+)CD25(+) T cells were present in PBMCs in the two groups, but fewer cells from atopic donors were CD4(+)CD25(+)CCR4(+) and more cells were CD4(+)CD25(+)CLA(+) compared to healthy donors.
CONCLUSION
Allergen-specific responses of grass allergic patients but not in non-atopic subjects are influenced by regulatory cytokines produced in response to the important allergens. Differences in CD4(+)CD25(+) T cell expression of chemokine receptors in allergic compared to non-atopic donors could suggest that the homing of CD4(+)CD25(+) T cells is important for the regulation of allergen-specific responses.
背景
在工业化国家,过敏性疾病的发病率正在增加,而导致耐受或过敏的免疫机制尚不清楚。具有抑制能力的细胞因子和 CD4+CD25+调节性 T 细胞被认为在变应原特异性反应中起核心作用。目的是确定主要草过敏原是否在过敏性和健康受试者中诱导产生抑制性细胞因子,并研究这些细胞因子对变应性反应的抑制作用。
方法
从健康和草过敏供体中分离外周血单核细胞 (PBMC),并用主要草过敏原 Phl p 1 或 Phl p 5 刺激。通过使用阻断抗体来确定内源性 IL-10 和/或 TGF-β对增殖和细胞因子产生的影响。此外,通过流式细胞术研究 CD4+CD25+T 细胞的数量及其趋化因子受体的表达。
结果
Phl p 1 和 Phl p 5 诱导 PBMC 培养物中来自特应性但不是非特应性供体的 IL-10 产生,从而下调增殖和细胞因子产生。两组中 PBMC 中存在相当频率的 CD4+CD25+T 细胞,但与健康供体相比,来自特应性供体的细胞中 CD4+CD25+CCR4+细胞较少,而 CD4+CD25+CLA+细胞较多。
结论
仅对草过敏患者的变应原特异性反应,而不是对非特应性患者的变应原特异性反应,受到针对重要过敏原产生的调节性细胞因子的影响。与非特应性供体相比,过敏性供体中 CD4+CD25+T 细胞表达趋化因子受体的差异可能表明 CD4+CD25+T 细胞的归巢对于调节变应原特异性反应很重要。