DIFFERENT IMBALANCES OF CYTOKINES IN NEMATODE INFECTIONS

该项目的长期目标是通过以下方式确定机制： 不同的线虫对肥大细胞产生相反的影响 细胞 巴西日本圆线虫（Nb）和旋毛虫（Ts） 引起显著的肠道肥大细胞增多症;相反， (Nd)不仅不会引起肥大细胞增多症， 肥大细胞增多症的症状 在正常骨骼的培养物中 骨髓，正常小鼠脾细胞的条件培养基（CM）（Nor-CM）或 Ts或Nb感染小鼠（Ts-CM或Nb-CM）支持肥大细胞的发育 来自骨髓祖细胞的细胞;脾细胞条件培养基 的Nd感染小鼠不能支持骨髓中肥大细胞的发育 培养并抑制活性CM的活性。 总体假设 Ts和Nb导致L3 T4 + T细胞失衡 有利于Th 2亚群，而Nd感染有利于Th 1亚群。 的 这种T细胞亚群失衡效应可能是不平衡的 细胞因子产生导致肥大细胞刺激和IgE产生 在Ts-和Nb-感染的小鼠中，以及在Nd-感染的小鼠中抑制这些事件， 小鼠 有人提出，IL-4的水平，一种Th 2细胞产物， 刺激肥大细胞发育和IgE合成，Ts 而Nb感染则使其降低。 这一假设将由以下人员进行检验： 测定Nor-CM的淋巴因子谱（IL-2、IFN-γ、IL-4、IL-5）， Ts-CM、Nb-CM和Nd-CM，通过测定细胞中这些淋巴因子的mRNA 感染动物，通过使用流式细胞术鉴定L3 T4 + 细胞，并通过评估纯化或重组细胞因子的作用， 和同源抗体对培养物中肥大细胞发育的影响。 结果 获得的结果将有助于制定控制肥大细胞的策略， 以及过敏和其他疾病状态下IgE的产生。

The long-term objective of this project is to determine the mechanisms by which different nematodes cause opposite effects on the production of mast cells. Nippostrongylus brasiliensis (Nb) and Trichinella spiralis (Ts) cause striking intestinal mastocytosis; by contrast, Nematospiroides dubius (Nd) not only fails to cause mastocytosis but also inhibits the development of mastocytosis following appropriate stimuli. In cultures of normal bone marrow, medium conditioned (CM) by spleen cells of normal mice (Nor-CM) or Ts-or Nb-infected mice (Ts-CM or Nb-CM) supports the development of mast cells from progenitors in bone marrow; medium conditioned by spleen cells of Nd-infected mice fails to support mast cell development in bone marrow cultures and inhibits the activity of active CM. The overall hypothesis for this proposal is that Ts and Nb cause an imbalance of L3T4+ T cells favoring the Th2 subset whereas Nd infection favors the Th1 subset. The effect of such imbalance of T cell subsets is likely to be imbalanced cytokine production leading to stimulation of mast cell and IgE production in Ts- and Nb-infected mice and inhibition of these events in Nd-infected mice. It is proposed that levels of IL-4, a Th2 cell product which stimulates mast cell development and IgE synthesis, will be increased by Ts and Nb but decreased by Nb infection. This hypothesis will be tested by determining the lymphokine profile (IL-2, IFN-gamma, IL-4, IL-5) of Nor-CM, Ts-CM, Nb-CM, and Nd-CM, by assaying for mRNA of these lymphokines in cells of infected animals, by using flow cytometry to identify subsets of L3T4+ cells, and by evaluating the effect of purified or recombinant cytokines and homologous antibodies on mast cell development in culture. Results obtained should be useful in developing strategies for control of mast cell and IgE production in allergic and other disease states.