Else K J, Hültner L, Grencis R K
Department of Cell & Structural Biology, University of Manchester, UK.
Parasite Immunol. 1992 Jul;14(4):441-9. doi: 10.1111/j.1365-3024.1992.tb00018.x.
BALB/K mice are usually resistant to infection with the intestinal nematode parasite Trichuris muris and exhibit a Th2 dominated (IL-5, IL-9) response. Conversely in B10.BR mice, which are unable to expel T. muris, Th1 type (IFN-gamma producing) cells predominate. We have manipulated the course of infection in these two strains of mice such that the period of host-parasite contact is extended in the former and curtailed in the latter. Extension of host-parasite contact in BALB/K mice beyond normal (day 21) resulted in the modulation of cytokines produced by in vitro concanavalin A (Con-A) stimulated MLNC away from IL-5 and IL-9 (Th2-type cytokines) in favour of the Th1-type cytokine IFN-gamma. Curtailment of host parasite contact in B10.BR mice to less than 21 days resulted in elevated production of IL-5 and IL-9 by MLNC in the absence of elevated IFN-gamma levels. Thus modulation of expulsion phenotype also modulates cytokine production by T-cells in the MLN draining the site of infection, with a Th2 response being associated with resistance and a Th1 type response with the inability to expel the parasite. Mechanisms by which the modulated cytokine profiles arise are discussed.
BALB/K小鼠通常对肠道线虫寄生虫毛首鞭形线虫的感染具有抵抗力,并表现出以Th2为主导(IL-5、IL-9)的反应。相反,在无法排出毛首鞭形线虫的B10.BR小鼠中,Th1型(产生IFN-γ)细胞占主导。我们对这两种品系小鼠的感染过程进行了调控,使得宿主与寄生虫接触的时间在前者中延长,而在后者中缩短。将BALB/K小鼠中宿主与寄生虫的接触时间延长至超过正常时间(第21天),导致体外伴刀豆球蛋白A(Con-A)刺激的肠系膜淋巴结细胞(MLNC)产生的细胞因子从IL-5和IL-9(Th2型细胞因子)向Th1型细胞因子IFN-γ转变。将B10.BR小鼠中宿主与寄生虫的接触时间缩短至少于21天,导致MLNC产生的IL-5和IL-9升高,而IFN-γ水平未升高。因此,排出表型的调节也会调节感染部位引流的肠系膜淋巴结中T细胞产生的细胞因子,Th2反应与抵抗力相关,而Th1型反应与无法排出寄生虫相关。文中讨论了调节后的细胞因子谱出现的机制。