IMMUNITY TO CRYPTOSPORIDIOSIS IN SIV INFECTED MACAQUES

感染 SIV 的猕猴对隐孢子虫病的免疫力

• 批准号: 6188702
• 负责人: SAUL r TZIPORI
• 金额: $ 27.07万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2003-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6188702
• 关键词: B lymphocyte; CD4 molecule; Cryptosporidium; Macaca mulatta; cryptosporidiosis; cytokine; enzyme linked immunosorbent assay; helper T lymphocyte; humoral immunity; immunocytochemistry; microorganism immunology; pathologic process; phenotype; polymerase chain reaction; simian immunodeficiency virus

This is the first resubmission of a research proposal in response to PA- 97-030 that focuses on defining the immunologic parameters involved in the development of chronic cryptosporidiosis in individuals with AIDS. The hypothesis to be tested is that a loss in mucosal CD4+ T cells and subsequent dysfunction of the mucosal associated immune system is responsible for chronic cryptosporidiosis in individuals with AIDS. To accomplish this, we will use a rhesus macaque model. Specific Aim 1 will examine the susceptibility of macaques to the development of chronic cryptosporidiosis at different stages of SIV infection. Specific Aim 2A of this proposal will examine the T and B lymphocyte responses associate with resolution of an acute Cryptosporidium parvum infection in normal, immunocompetent macaques. These studies will utilize FACS analysis, immunohistochemistry, ELISA, in vitro proliferative assays and RT-PCR analysis to examine the humoral response and the phenotype, cytokine profile and proliferative response of mucosal and peripheral T lymphocytes in non-SIV infected macaques with resolving cryptosporidiosis. Specific Aim 2B of this proposal will determine if there are quantitative and/or qualitative differences in T and/or B lymphocyte responses that are associated with the development of chronic cryptosporidiosis in SIV-infected macaques. These studies will utilize the same techniques listed above for Specific Aim 2A to examine the humoral response and the phenotype, cytokine profile and proliferative response of mucosal and peripheral T lymphocytes in SIV-infected macaques with acute and chronic cryptosporidiosis. The studies proposed herein represent long term research goals aimed at enhancing our knowledge of the immune mechanism(s) involved in the control of cryptosporidiosis, and the underlying reasons for failure in the SIV/HIV-infected host. An understanding of this mechanism is important for the derivation of immunotherapeutic strategies that may be necessary to control chronic cryptosporidiosis in patients with AIDS.

这是研究建议的第一次重新提交，以应对PA- 97-030重点是定义涉及的免疫学参数 艾滋病患者中慢性隐孢子虫病的发展。 要检验的假设是粘膜CD4+ T细胞和 随后粘膜相关免疫系统功能障碍是 负责艾滋病患者的慢性隐孢子虫病。到 这样做，我们将使用恒河猴模型。具体目标1将 检查猕猴对慢性发展的敏感性 SIV感染不同阶段的隐孢子虫病。特定目标2a 该提案将检查T和B淋巴细胞反应关联 通过在正常情况下消除急性隐孢子虫感染 免疫能力猕猴。这些研究将利用FACS分析， 免疫组织化学，ELISA，体外增殖测定和RT-PCR 分析检查体液反应和表型，细胞因子 粘膜和周围T的曲线和增殖反应 在非SIV感染猕猴的淋巴细胞和分辨率 隐孢子虫病。该提案的特定目标2B将确定是否是否 t和/或b存在定量和/或定性差异 与慢性发展有关的淋巴细胞反应 SIV感染的猕猴中的隐孢子虫病。这些研究将利用 上面列出的针对特定目标2a的相同技术来检查 体液反应和表型，细胞因子谱和增殖 SIV感染的粘膜和周围T淋巴细胞的反应 与急性和慢性隐孢子虫病的猕猴。研究提出 此处代表了旨在增强我们的长期研究目标 了解控制的免疫机制 隐孢子虫病，以及造成失败的根本原因 SIV/HIV感染的宿主。对这种机制的理解很重要 为了推导可能是必要的免疫治疗策略 控制艾滋病患者的慢性隐孢子虫病。