Human CD4+CD25+ T cells derived from the majority of atopic donors are able to suppress TH1 and TH2 cytokine production
Human CD4+CD25+ T cells derived from the majority of atopic donors are able to suppress TH1 and TH2 cytokine production
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DOI：
10.1067/mai.2003.1412
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发表时间：
2003-04-01
影响因子：
14.2
通讯作者：
Saloga, J
中科院分区：
文献类型：
--
作者：
Bellinghausen, I;Klostermann, B;Saloga, J
背景资料：最近，已经确定具有调节能力的CD 4（+）CD 25（+）T细胞存在于人外周血中，抑制预活化的CD 4（+）CD 25（-）应答T细胞的同种异体增殖和细胞因子产生。本研究的目的是分析在过敏原特异性环境中，这种调节性CD 4（+）CD 25（+）在特应性个体中T细胞也存在并正常发挥功能，特别是关于T（H）2细胞因子的抑制。为此目的，来自对草或桦树花粉过敏的供体的CD 4（+）CD 25（-）或CD 4（+）CD 25（+）T细胞在自体的、成熟的、单核细胞衍生的、变应原致敏的树突状细胞的存在下，刺激来自正常人（主要患有鼻炎）或健康的非特应性供体的CD 4（+）CD 25（+）T细胞，并在再刺激期间将预活化的CD 4（+）CD 25（-）T细胞加入到CD 4（+）CD 25（-）T细胞中。来自非特应性供体和大多数研究患者的CD 4（+）CD 25（+）T细胞增殖较差，产生较少的细胞因子，抑制CD 4（+）CD 25（-）T细胞的增殖和T（H）1（IFN-γ）和T（H）2（IL-4和IL-5）细胞因子的产生，但不抑制IL-10的产生。CD 4（+）CD 25（+）T细胞对CD 4（+）CD 25（-）T细胞的抑制至少部分是抗原非特异性的，并且使用抗IL-10、抗转化生长因子β或抗细胞毒性T淋巴细胞相关抗原4 mAb时不可逆，但使用IL-2时可逆。在某些特应性患者中，预活化的CD 4（+）CD 25（+）T细胞可重复地显示出强烈的增殖反应，产生比CD 4（+）CD 25（-）T细胞更高量的IL-4和IL-10，并且仅抑制CD 4（+）CD 25（-）T细胞的IFN-γ产生。这些数据表明，调节性CD 4（+）CD 25（+）T细胞在大多数过敏性鼻炎患者中存在并发挥功能，能够抑制T（H）1和T（H）2细胞因子的产生。
Background: Recently, it has been established that CD4(+)CD25(+) T cells with regulatory capacity are present in human peripheral blood, inhibiting allogeneic proliferation and cytokine production of preactivated CD4(+)CD25(-) responder T cells.Objective: The aim of this study was to analyze in an allergen-specific setting whether such regulatory CD4(+)CD25(+) T cells also exist and function normally in atopic individuals, especially concerning the inhibition of T(H)2 cytokines.Methods: For this purpose, CD4(+)CD25(-) or CD4(+)CD25(+) T cells from donors allergic to grass or birch pollen (mainly with rhinitis) or from healthy nonatopic donors were stimulated in the presence of autologous, mature, monocyte-derived, allergen-pulsed dendritic cells, and the preactivated CD4(+)CD25(+) T cells were added to CD4(+)CD25(-) T cells during restimulation.Results: CD4(+)CD25(+) T cells from the nonatopic donors and from the majority of the patients investigated proliferated poorly, produced fewer cytokines, and inhibited the proliferation and T(H)1 (IFN-gamma) and T(H)2 (IL-4 and IL-5) cytokine production of CD4(+)CD25(-) T cells but not IL-10 production. The suppression of CD4(+)CD25(-) T cells by CD4(+)CD25(+) T cells was at least partially antigen unspecific and not reversible with anti-IL-10, anti-transforming growth factor beta, or anti-cytotoxic T lymphocyte-associated antigen 4 mAb but was reversible with IL-2. In some atopic patients preactivated CD4(+)CD25(+) T cells reproducibly showed strong proliferative responses, produced higher amounts of IL-4 and IL-10 than CD4(+)CD25(-) T cells, and suppressed only the IFN-gamma production of CD4(+)CD25(-) T cells.Conclusion: These data indicate that regulatory CD4(+)CD25(+) T cells are present and functional in most atopic patients with allergic rhinitis and are able to inhibit T(H)1, as well as T(H)2, cytokine production.