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 哪些不同的线虫会对桅杆的生产产生相反的影响 细胞。巴西尼波斯特罗线虫(Nb)和旋毛虫(Ts) 引起显著的肠道肥大细胞增多症；相比之下，杜氏线虫 (ND)不仅不会引起肥大细胞增多症，而且还会抑制发育 在适当的刺激下肥大细胞增多症。在正常骨的培养中 骨髓，由正常小鼠的脾细胞(NOR-CM)培养(CM)或 感染TS或NB的小鼠(TS-CM或NB-CM)支持肥大的发育 骨髓祖细胞来源的细胞；脾细胞条件培养液 未能支持骨髓中肥大细胞的发育 培养和抑制活性CM的活性。总体假设 因为这一建议是TS和Nb导致L3T4T细胞失衡 偏向Th2亚群，而ND感染偏向Th1亚群。这个 这种T细胞亚群失衡的影响可能是不平衡的 细胞因子的产生刺激肥大细胞和IgE的产生 在感染TS和Nb的小鼠中以及在ND感染中对这些事件的抑制 老鼠。据认为，Th2细胞产物IL-4的水平 刺激肥大细胞发育和IgE合成，TS将增加 和Nb，但受Nb感染后下降。这一假设将通过以下方式检验 测定NOR-CM的淋巴因子谱(IL-2、干扰素-γ、IL-4、IL-5)， TS-CM、NB-CM和ND-CM，通过检测细胞中这些淋巴因子的mRNA 通过使用流式细胞术识别L3T4亚群 细胞，并通过评估纯化或重组细胞因子的效果 以及培养中肥大细胞发育的同源抗体。结果 所获得的结果将有助于制定控制肥大细胞的策略 过敏和其他疾病状态下的IgE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.