Calder V L, Jolly G, Hingorani M, Adamson P, Leonardi A, Secchi A G, Buckley R J, Lightman S
Department of Clinical Ophthalmology, Institute of Ophthalmology, UCL, London, UK.
Clin Exp Allergy. 1999 Sep;29(9):1214-22. doi: 10.1046/j.1365-2222.1999.00585.x.
Activated CD4+ T cells, mast cells and eosinophils are the main cytokine-producing cell-types infiltrating the conjunctiva during chronic allergic eye diseases. Interactions between these cells are thought to play an important immunopathogenic role in these disorders (giant papillary conjunctivitis; vernal keratoconjunctivitis; atopic keratoconjunctivitis).
The objective was to compare the cytokine profiles of conjunctival T-cell lines from patients with different forms of chronic allergic eye disease.
T cells were isolated from conjunctival biopsies and non-specifically expanded into lines. The lines were immunophenotyped by flow cytometry. Cytokine production was quantified by immunoassays and more sensitive molecular techniques were used to investigate cytokine mRNA expression to identify the presence of interleukin (IL) -2, IL-4 and interferon (IFN) -gamma transcripts.
Following four to six rounds of stimulation, the conjunctival T-cell populations were CD3+ (> 93%), with variable levels of CD4 and CD8 expression. All were HLA-DR+ (> 80%) with some HLA-DQ expression. Conjunctival T-cell lines from atopic keratoconjunctivitis produced selective increases in IFN-gamma, IL-10 and IL-13 (P<0.01), those from vernal keratoconjunctivitis produced increased IL-5 (P<0.01) whereas T-cell lines from giant papillary conjunctivitis produced only low levels of cytokines. IL-4 was only detected at the mRNA level and was expressed in four out of five T-cell lines in the vernal keratoconjunctivitis group. In contrast there was moderate to strong expression of IFN-gamma in five out of six T-cell lines in atopic keratoconjunctivitis.
Different patterns of T-cell cytokine profiles were observed for each disease, with low-level, non-polarized cytokine production in giant papillary conjunctivitis, a TH2-like profile in vernal keratoconjunctivitis and a shift towards a TH1-like profile in atopic keratoconjunctivitis.
活化的CD4+ T细胞、肥大细胞和嗜酸性粒细胞是慢性过敏性眼病期间浸润结膜的主要细胞因子产生细胞类型。这些细胞之间的相互作用被认为在这些疾病(巨大乳头性结膜炎、春季角结膜炎、特应性角结膜炎)中起重要的免疫致病作用。
比较不同形式慢性过敏性眼病患者结膜T细胞系的细胞因子谱。
从结膜活检组织中分离T细胞并将其非特异性扩增为细胞系。通过流式细胞术对细胞系进行免疫表型分析。通过免疫测定法对细胞因子产生进行定量,并使用更灵敏的分子技术研究细胞因子mRNA表达,以鉴定白细胞介素(IL)-2、IL-4和干扰素(IFN)-γ转录本的存在。
经过四到六轮刺激后,结膜T细胞群体为CD3+(>93%),CD4和CD8表达水平各异。所有细胞均为HLA-DR+(>80%),并有一些HLA-DQ表达。特应性角结膜炎的结膜T细胞系产生的IFN-γ、IL-10和IL-13选择性增加(P<0.01),春季角结膜炎的结膜T细胞系产生的IL-5增加(P<0.01),而巨大乳头性结膜炎的T细胞系仅产生低水平的细胞因子。IL-4仅在mRNA水平检测到,在春季角结膜炎组的五个T细胞系中有四个表达。相比之下,特应性角结膜炎的六个T细胞系中有五个IFN-γ表达为中度至强阳性。
每种疾病观察到不同模式的T细胞细胞因子谱,巨大乳头性结膜炎为低水平、非极化的细胞因子产生,春季角结膜炎为TH2样谱,特应性角结膜炎则向TH1样谱转变。