Metwali A, Elliott D, Mathew R, Blum A, Weinstock J V
Department of Internal Medicine, University of Iowa, Iowa City 52242.
J Immunol. 1993 Jan 15;150(2):536-42.
Th cells within the granulomas of murine schistosomiasis mansoni produce IL-5, which is essential for granuloma eosinophil growth and development. The mechanisms regulating granuloma IL-5 production are unknown. The granulomas also make IL-2 in small quantities. rIL-2 therapy stimulates eosinophilia and IL-5 synthesis. Therefore, we studied the effect of IL-2 on IL-5 production within the liver granulomas of murine Schistosoma mansoni. Dispersed granuloma cells and intact granulomas cultured in vitro released IL-5. Adding anti-IL-2 or anti-IL-2R to the cultures, to block IL-2 activity, significantly inhibited IL-5 production. However, supplementing the cultures with small quantities of rIL-2 markedly stimulated IL-5 release in a dose-dependent fashion. Blocking anti-IL-4 mAb had no effect. Also, granuloma T cells were isolated by FACS. These highly purified T cells produced IL-5 both in the presence and absence of plate-bound anti-CD3. Once again, the IL-5 production was dependent on IL-2. The requirement of IL-2 for normal IL-5 production was not dependent on an IL-2-induced expansion of the IL-5-producing, T lymphocyte population. Thus, IL-2 mediates T cell interactions within the granuloma that regulate granuloma IL-5 secretion.
曼氏血吸虫病小鼠肉芽肿内的Th细胞产生IL-5,这对肉芽肿嗜酸性粒细胞的生长和发育至关重要。调节肉芽肿IL-5产生的机制尚不清楚。肉芽肿也少量产生IL-2。重组IL-2治疗可刺激嗜酸性粒细胞增多和IL-5合成。因此,我们研究了IL-2对曼氏血吸虫病小鼠肝脏肉芽肿内IL-5产生的影响。体外培养的分散肉芽肿细胞和完整肉芽肿可释放IL-5。向培养物中添加抗IL-2或抗IL-2R以阻断IL-2活性,可显著抑制IL-5的产生。然而,向培养物中补充少量重组IL-2可显著以剂量依赖方式刺激IL-5释放。阻断抗IL-4单克隆抗体无作用。此外,通过荧光激活细胞分选术分离肉芽肿T细胞。这些高度纯化的T细胞在存在和不存在板结合抗CD3的情况下均产生IL-5。同样,IL-5的产生依赖于IL-2。IL-2对正常IL-5产生的需求不依赖于IL-2诱导的产生IL-5的T淋巴细胞群体的扩增。因此,IL-2介导肉芽肿内调节肉芽肿IL-5分泌的T细胞相互作用。