Jung T, Witzak K, Dieckhoff K, Zachmann K, Heidrich S, Aversa G, Neumann C
Department of Dermatology, University Göttingen, Germany.
Clin Exp Allergy. 1999 Feb;29(2):207-16. doi: 10.1046/j.1365-2222.1999.00482.x.
Although it is well established that T cells derived from patients with atopic diseases produce low levels of interferon-gamma (IFN-gamma), the mechanisms responsible for this phenomenon are poorly understood.
To elucidate whether IFN-gamma production may be restored by co-stimulatory molecules known to increase IFN-gamma production in vitro. Further, to investigate whether deficient IFN-gamma production is associated with disease activity.
Purified peripheral T cells obtained from patients with severe atopic dermatitis (AD), individuals with a history but no symptoms of AD and healthy control subjects were activated with anti-CD3 MoAbs in the presence or absence of anti-CD28 MoAbs, interleukin (IL-) 12, IL-2, IL-15 or IL-18. IFN-gamma production was determined at the single cell level by flow cytometry, as well as by ELISA.
Activated T cells from patients with severe AD produced less IFN-gamma than T cells from healthy control individuals. IL-12 or engagement of CD28 enhanced IFN-gamma production in both healthy and atopic T cells. However, absolute values of IFN-gamma were still different. IL-2, IL-15 and IL-18 did not restore IFN-gamma production. T cells from individuals with a history of AD produced more IFN-gamma than those from subjects with severe AD, but less than T cells from healthy individuals. Atopic T cells expressed regular levels of CD3, CD28 and Stat4, the main signal transducer and activator of transcription for IL-12. IL-4, IL-10 and TGF-beta production by T cells were not different between healthy and atopic individuals.
IFN-gamma deficiency in atopic T cells is not due to a lack of responsiveness to CD28, IL-12, IL-2, IL-15 or IL-18. T cell-derived cytokines able to antagonize IFN-gamma do not contribute to decreased IFN-gamma production. The extent of IFN-gamma deficiency seems to be dependent on disease activity.
尽管已经明确，来自特应性疾病患者的T细胞产生的干扰素-γ（IFN-γ）水平较低，但导致这一现象的机制仍知之甚少。
阐明已知在体外可增加IFN-γ产生的共刺激分子是否能恢复IFN-γ的产生。此外，研究IFN-γ产生不足是否与疾病活动相关。
从重度特应性皮炎（AD）患者、有AD病史但无症状的个体以及健康对照者中获取纯化的外周血T细胞，在有或无抗CD28单克隆抗体、白细胞介素（IL-）12、IL-2、IL-15或IL-18存在的情况下，用抗CD3单克隆抗体激活这些T细胞。通过流式细胞术以及酶联免疫吸附测定法在单细胞水平测定IFN-γ的产生。
重度AD患者激活的T细胞产生的IFN-γ比健康对照个体的T细胞少。IL-12或CD28的激活均增强了健康和特应性T细胞中IFN-γ的产生。然而，IFN-γ的绝对值仍存在差异。IL-2、IL-15和IL-18未能恢复IFN-γ的产生。有AD病史个体的T细胞产生的IFN-γ比重度AD患者的T细胞多，但比健康个体的T细胞少。特应性T细胞表达正常水平的CD3、CD28和Stat4，Stat4是IL-12的主要信号转导和转录激活因子。健康个体和特应性个体的T细胞产生的IL-4、IL-10和转化生长因子-β没有差异。
特应性T细胞中IFN-γ缺乏并非由于对CD28、IL-12、IL-2、IL-15或IL-18反应不足。能够拮抗IFN-γ的T细胞衍生细胞因子对IFN-γ产生减少没有作用。IFN-γ缺乏的程度似乎取决于疾病活动。
