Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy
Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy
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DOI：
10.1067/mai.2003.1570
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发表时间：
2003-06-01
影响因子：
14.2
通讯作者：
Durham, SR
中科院分区：
文献类型：
--
作者：
Francis, JN;Till, SJ;Durham, SR
背景资料：免疫治疗涉及调节过敏原特异性T细胞反应，无论是T（H）2至T（H）1免疫偏离，还是在蜂毒治疗的患者中，诱导CD 4（+）CD 25（+）T细胞产生IL-10。IL-111产生的CD 4（+）CD 25（+）调节性T细胞在许多小鼠免疫病理学模型中已成为免疫耐受的潜在介质。目的：本研究的目的是评估IL-10产生和CD 4（+）CD 25（+）T细胞在对草花粉免疫疗法的应答中的作用。从草花粉免疫治疗1年后的患者和匹配的未治疗的特应性和健康对照受试者中分离PBMC。在体外用草豆蔻刺激6天后，测量IL-10、IL-5、IL-4和IFN-γ的产生以及CD 4（+）CD 25（+）T细胞的增殖和数量。然后用佛波醇12-肉豆蔻酸酯13-乙酸酯和离子霉素再刺激T细胞5小时，并通过流式细胞术评估细胞内IL-10。结果：接受免疫治疗的患者产生的IL-10明显多于特应性对照组（接受免疫治疗的患者，116 +/- 21 pg/mL [n = 11];特应性患者）。30 +/- 5 pg/mL [n = 11]; P <0.001），免疫治疗组在变应原刺激后鉴定的CD 4（+）CD 25（+）细胞数量也更高。在两个对照组中，CD 4（+）CD 25（+）T细胞的数量与通过增殖测量的活化呈正相关，但在免疫治疗组中不相关。此外，只有接受免疫治疗的患者的T细胞对细胞内IL-10呈阳性，并且这些细胞几乎完全是CD 4（+）CD 25（+）cells.Conclusion：草花粉免疫治疗导致一群表达IL-10（+）CD 4（+）CD 25（+）表型的循环T细胞响应变应原再刺激。
Background: Immunotherapy involves the modulation of allergen-specific T-cell responses, either T(H)2-to-T(H)1 immune deviation or, in bee venom-treated patients, induction of IL-10 production by CD4(+)CD25(+) T cells. IL-111-producing CD4(+)CD25(+) regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology.Objective: The aim of this study was to evaluate the role of IL10 production and CD4(+)CD25(+) T cells in the response to grass pollen immunotherapy.Methods: PBMCs were isolated from patients after 1 year of grass pollen immunotherapy and from matched untreated atopic and healthy control subjects. After 6 days of in vitro stimulation with Phleum pratense, production of IL-10, IL-5, IL-4, and IFN-gamma and proliferation and numbers of CD4(+)CD25(+) T cells were measured. T cells were then stimulated for a further 5 hours with phorbol 12-myristate 13-acetate and ionomycin and assessed for intracellular IL-10 by means of flow cytometry.Results: Patients undergoing immunotherapy produced significantly, more IL-10 than atopic control subjects (patients undergoing immunotherapy, 116 +/- 21 pg/mL [n = 11]; atopic patients. 30 +/- 5 pg/mL [n = 11]; P < .001), and the number of CD4(+)CD25(+) cells identified after allergen stimulation was also greater in the immunotherapy group. The numbers of CD4(+)CD25(+) T cells correlated positively with activation as measured by proliferation in both of the control groups but not in the immunotherapy group. Moreover, only T cells from patients undergoing immunotherapy were positive for intracellular IL-10, and these were almost exclusively CD4(+)CD25(+) cells.Conclusion: Grass pollen immunotherapy results in a population of circulating T cells that express the IL-10(+)CD4(+)CD25(+) phenotype in response to allergen restimulation.