MOUSE HEPATITIS VIRUS-ASSOCIATED IMMUNE DYSFUNCTION

小鼠肝炎病毒（MHV）感染实验小鼠发生在高 在许多生物医学学科中， 通常使用。 用MHV感染淋巴细胞供体可导致T 细胞功能障碍，如体外增殖和细胞因子所反映的 生产 然而，细胞因子在MHV发病机制中的作用 小鼠通过自然途径暴露后的感染尚未得到解决。 一旦这些分子的作用被牢固地确立， 以鉴定分泌细胞因子的细胞类型， 他们所从事的工作。 长期目标是发展 控制和预防地方性MHV的合理策略 实验室小鼠群体。 本研究的具体目的是：1.为了进一步表征 细胞因子在MHV发病机制中的作用，使用细胞因子免疫疗法或 诱导方法和细胞因子缺失，和2.来识别细胞类型 产生有益的细胞因子以及那些被这些细胞因子激活的细胞因子， 可溶性介质 本提案的目的是检验以下假设： 活化的T细胞释放的某些细胞因子，以及其他细胞 型，可能介导MHV感染的良性结果。 干扰素γ 和白细胞介素4是主要感兴趣的分子。 导频数据 提示CD 4 + T细胞效应功能可能与 MHV感染的病理学和阴性结果。 T的这两个方面 细胞生物学难以分离;然而，药物和/或 抗体诱导的细胞缺失结合细胞因子免疫疗法将 开始暗示我们的假设是否有价值。 的可用性 基因定义小鼠，重组细胞因子，单克隆抗体 与这些分子和细胞特异性药物反应， 病毒和免疫系统的体内相互作用是可行的。

Mouse hepatitis virus (MHV) infection of laboratory mice occurs at high prevalence and impacts heavily on many biomedical disciplines in which mice are commonly used. Infection of lymphocyte donors with MHV results in T cell dysfunction, as reflected by in vitro proliferation and cytokine production. However, the role of cytokines in the pathogenesis of MHV infection after exposure of mice by natural routes has not been addressed. Once the role of these molecules has been firmly established, efforts will be made to identify the cell type(s) secreting cytokines and the cell type(s) upon which they act. The long-term goal is the development of rational strategies for control and prevention of enzootic MHV in laboratory mouse colonies. The specific aims of the proposed research are: 1. to characterize further the role of cytokines in MHV pathogenesis, using cytokine immunotherapy or induction methods and cytokine deletion, and 2. to identify the cell types producing beneficial cytokines as well as those that are activated by these soluble mediators. The objective of the current proposal is to test the hypothesis that certain cytokines released by activated T cells, as well as other cell types, may mediate benign outcome of infection with MHV. Interferon gamma and interleukin 4 are the molecules of primary interest. Pilot data suggest that effector function of CD4+ T cells may be associated with pathology and negative outcome of MHV infection. These two aspects of T cell biology are difficult to separate; however, drug- and/or antibody-induced cell deletion combined with cytokine immunotherapy will begin to suggest whether our hypothesis has merit. The availability of genetically defined mice, recombinant cytokines, monoclonal antibodies reactive with these molecules and cell-specific drugs renders an approach to the in vivo interactions of virus and the immune system feasible.