Sasaki G, Satoh T, Yokozeki H, Katayama I, Nishioka K
Department of Dermatology, Tokyo Medical and Dental University, Tokyo, Japan.
Cell Immunol. 2000 Aug 1;203(2):124-33. doi: 10.1006/cimm.2000.1677.
Blood and tissue eosinophilia is obtained when mice pretreated with cyclophosphamide (CY) and sensitized with picryl chloride are challenged on each ear lobe on day 13. To gain important insights into the cellular mechanisms involved in CY-induced eosinophilia in the contact-sensitivity reaction, we examined the cytokine profile expressed in regional lymph node cells and spleen cells. CY pretreatment 2 days before sensitization enhanced expression of IL-4 mRNA in the regional lymph node cells more strongly than expressions of both IL-2 and IFN-gamma mRNA on day 13. Five days after sensitization, spleen cells expressed IL-5 mRNA and produced IL-5 in vitro. Depletion of CD4(+) cells from spleen cells completely abrogated the secretory capacity of IL-5. In vivo blocking of IL-5 on day 3 entirely inhibited spleen, bone marrow, and subsequent blood eosinophilia. When immune lymph node cells prepared on day 13 were stimulated with hapten-modified cells in vitro, the level of IL-4 secreted in the culture supernatant was enhanced by CY pretreatment, but that of IL-2 was not. One important result was that IL-5 was not produced in response to in vitro stimulation, despite the fact that marked eosinophil infiltration in the dermis was observed in vivo. Thus, eosinophilopoiesis was stimulated by IL-5-producing CD4(+) immune T cells that were present in the eosinophil production site, particularly in the spleen before elicitation. In contrast, eosinophil recruitment into the dermis in the efferent phase can be induced without production of IL-5 from lymphocytes.
当用环磷酰胺（CY）预处理并经苦味酸氯致敏的小鼠在第13天对每个耳垂进行激发时，可出现血液和组织嗜酸性粒细胞增多。为了深入了解接触敏感性反应中CY诱导嗜酸性粒细胞增多所涉及的细胞机制，我们检测了局部淋巴结细胞和脾细胞中表达的细胞因子谱。致敏前2天进行CY预处理，在第13天比IL-2和IFN-γ mRNA的表达更强烈地增强了局部淋巴结细胞中IL-4 mRNA的表达。致敏后5天，脾细胞表达IL-5 mRNA并在体外产生IL-5。从脾细胞中去除CD4(+)细胞完全消除了IL-5的分泌能力。在第3天体内阻断IL-5完全抑制了脾脏、骨髓以及随后的血液嗜酸性粒细胞增多。当用半抗原修饰的细胞在体外刺激第13天制备的免疫淋巴结细胞时，CY预处理可提高培养上清液中分泌的IL-4水平，但IL-2水平未提高。一个重要的结果是，尽管在体内观察到真皮中有明显的嗜酸性粒细胞浸润，但体外刺激并未产生IL-5。因此，嗜酸性粒细胞生成是由产生IL-5的CD4(+)免疫T细胞刺激的，这些细胞存在于嗜酸性粒细胞生成部位，特别是在激发前的脾脏中。相反，在传出阶段嗜酸性粒细胞募集到真皮中可以在淋巴细胞不产生IL-5的情况下诱导。
