IMMUNE RESPONSE OF THE GUT AND LIVER IN TOXOPLASMOSIS

弓形虫的自然感染是通过口服途径。 因此，寄生虫最初的入侵是通过宿主的肠道。 许多速殖子可能会被困在肝脏中。 因此，我们认为， 肠相关淋巴组织（GALT）（上皮内 淋巴细胞，固有层淋巴细胞，派伊尔淋巴细胞 斑块、肠系膜淋巴结）和肝脏在 对经口感染T.刚地。 然而，在这方面， 关于肠道和肝脏中免疫反应的信息， T.缺乏弓形虫感染。 最近，我发现了一个关键的作用， 小淋巴结上皮内淋巴细胞中的γ/δ T细胞 肠道和情人体内的T细胞在预防子宫内膜增生中的作用 速殖子在这些器官在经口感染的早期阶段。 此外，我还发现，α/β T细胞对 经口感染，毒性较小，但对经口感染有害。 用毒性更强的T.刚地。 关于基因 我的初步数据揭示了T细胞在小鼠易感性中的关键作用， 细胞在发展中的坏死，在小肠发生 仅在经口感染的早期易感小鼠中。 我推测，在GALT和肝脏的T细胞的功能， 经口感染T.弓形虫在 决定感染的结果。 总体具体目标 这项提议是分析肠道中产生的T细胞的功能， 和肝脏组织的病理改变。弓形虫 小鼠，并确定T细胞在这些器官中的作用， 弓形虫病的发病机制与弓形虫毒力的关系 寄生虫和宿主的遗传易感性。 这些长期 目标将通过获得以下方面的信息来实现：1） GALT和肝脏中的T细胞亚群。 2)鉴定 负责保护性或“有害”免疫的T细胞亚群 应答 3)T细胞的细胞因子产生和细胞毒活性 负责保护性或“有害”免疫应答的亚群。 4)细胞因子在保护T细胞“有害”活性中作用 子集。 这些研究产生的数据将有助于 通过更好地了解这一建议的长期目标， GALT和肝脏中T细胞在抵抗 T.弓形虫病的发病机制与 寄生虫的毒力和宿主的遗传易感性。

Natural infection with Toxoplasma gondii is by the peroral route. Thus, initial invasion by the parasite is through the gut of the host. Many tachyzoites are then likely to be trapped in the liver. Therefore, it is likely that gut-associated lymphoid tissue (GALT) (intraepithelial lymphocytes, lamina propria lymphocytes, lymphocytes in the Peyer's patches, mesenteric lymph nodes) and the liver play critical roles in resistance against peroral infection with T. gondii. However, information regarding the immune response in the gut and liver during T. gondii infection is lacking. Recently, I found a critical role of gamma/delta T cells in the intraepithelial lymphocytes of the small intestines and T cells in the lover in prevention of proliferation of tachyzoites in these organs during the early stage of peroral infection. In addition, I also found that alpha/beta T cells are protective against peroral infection with a less virulent strain but detrimental in peroral infection with a more virulent strain of T. gondii. In relation to genetic susceptibility of mice, my preliminary data reveal a critical role of T cells in development of necrosis in the small intestines which occurred only in the susceptible mice during the early stage of peroral infection. I hypothesize that the functions of T cells of the GALT and liver during the early stage of peroral infection with T. gondii are critical in determining the outcome of the infection. The overall specific aim of this proposal is to analyze the function of T cells generated in the gut and liver during the early stage of peroral infection with T. gondii in mice and to determine the role of T cells in these organs in resistance against and pathogenesis of toxoplasmosis in relation to the virulence of the parasite and genetic susceptibility of the host. These long term objectives will be addressed by gaining information on: 1) changes in populations of T cell subsets in the GALT and liver. 2) Identification of T cell subset(s) responsible for protective or "harmful" immune responses. 3) cytokine production and cytotoxic activity of the T cell subset(s) responsible for the protective or "harmful" immune responses. 4) the role of cytokine(s) in protective of "harmful" activity of T cell subset(s). The data generated from these studies will contribute to the long term aims of this proposal by gaining a better understanding of the roles and functions of T cells in the GALT and liver in resistance against T. gondii and in the pathogenesis of toxoplasmosis in relation to the virulence of the parasite and genetic susceptibility of the host.