Morikawa H, Nagashima S
Department of Microbiology, Dokkyo University School of Medicine, Tochigi, Japan.
Clin Exp Allergy. 2000 Mar;30(3):383-92. doi: 10.1046/j.1365-2222.2000.00713.x.
B7-1 (CD80) and B7-2 (CD86), which are costimulatory molecules in T-cell activation, play important roles in the differentiation of TH1- or TH2-phenotypes. These molecules were also suggested to play important roles in sensitization to a cedar pollen antigen by blocking studies using neutralizing antibodies, but there have been very few studies concerning the effects following induction by antigen.
In this study, we investigated the roles of B7-1 and B7-2 in the differentiation of TH1 and TH2 subsets after stimulation with the antigen in subjects with cedar pollinosis.
Skin-prick test was performed in nine subjects with pollinosis and in nine normal controls. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with Japanese cedar pollen extract. After in vitro stimulation, the expression of CD80 and CD86 on CD19+ cells was analysed by two-colour flow cytometry. Culture supernatants were collected for all subjects and the production of type 1 and type 2 cytokines was measured by ELISA.
After in vitro stimulation, the expression of CD80 (B7-1) was upregulated in both pollinosis and control subjects, but no significant difference was observed between the two groups. On the other hand, CD86 (B7-2) was significantly upregulated following stimulation in pollinosis subjects (P = 0.02). A significantly higher level of IL-5 (P = 0.04) was produced by PBMCs of pollinosis subjects than by those of normal controls. A significantly higher level of interferon (IFN)-gamma (P = 0.03) was produced by PBMCs of normal controls than by those of pollinosis subjects.
These results indicated that TH2 response was predominant in pollinosis subjects, and that CD19+ cells of pollinosis subjects expressed higher levels of B7-2 than those of control subjects after in vitro stimulation. In pollinosis subjects, B7-2 rather than B7-1 may be the costimulatory molecule involved in allergen-induced activation of PBMCs.
B7-1（CD80）和B7-2（CD86）是T细胞活化中的共刺激分子，在TH1或TH2表型的分化中起重要作用。通过使用中和抗体的阻断研究也表明这些分子在对雪松花粉抗原的致敏中起重要作用，但关于抗原诱导后的效应的研究非常少。
在本研究中，我们调查了B7-1和B7-2在雪松花粉症患者中抗原刺激后TH1和TH2亚群分化中的作用。
对9名花粉症患者和9名正常对照进行皮肤点刺试验。分离外周血单核细胞（PBMC）并用日本雪松花粉提取物刺激。体外刺激后，通过双色流式细胞术分析CD19+细胞上CD80和CD86的表达。收集所有受试者的培养上清液，并用ELISA测量1型和2型细胞因子的产生。
体外刺激后，花粉症患者和对照受试者中CD80（B7-1）的表达均上调，但两组之间未观察到显著差异。另一方面，花粉症患者刺激后CD86（B7-2）显著上调（P = 0.02）。花粉症患者的PBMC产生的IL-5水平显著高于正常对照（P = 0.04）。正常对照的PBMC产生的干扰素（IFN）-γ水平显著高于花粉症患者（P = 0.03）。
这些结果表明，TH2反应在花粉症患者中占主导地位，并且体外刺激后花粉症患者的CD19+细胞表达的B7-2水平高于对照受试者。在花粉症患者中，B7-2而非B7-1可能是参与变应原诱导的PBMC活化的共刺激分子。
