IMMUNOLOGY OF BACTERIAL PNEUMONIA IN HTLV-II INFECTION

HTLV-II 感染中细菌性肺炎的免疫学

• 批准号: 6046134
• 负责人: Gary A Jarvis
• 金额: $ 25.66万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6046134
• 关键词: B lymphocyte; CD antigens; CD4 molecule; CD8 molecule; T lymphocyte; antibody; bacterial pneumonia; blood donor; clinical research; cytokine; disease /disorder proneness /risk; enzyme linked immunosorbent assay; flow cytometry; human T cell lymphotropic virus type 2; human subject; immunoglobulin G; immunopathology; interleukin 2; macrophage; respiratory disorder epidemiology; tissue /cell culture; vaccines

DESCRIPTION (Adapted from the Applicant's Abstract): This projects seeks to understand the immunologic basis for the epidemiological outcome observation of an increased incidence of bacterial pneumonia in HTLV-II-infected blood donors. In a study of persons with both HTLV-II seropositivity and intravenous drug use, an increased risk for bacterial pneumonia compared to patients with neither risk was found. A similar finding of increased risk for bacterial pneumonia in HTLV-II-infected individuals was observed in a clinical outcome analysis of blood donors who participated in a Retroviral Epidemiological Donors Study. Since the cell tropism of HTLV-II infection includes CD4+ and CD8+ T cells, B cells and monocytes, the investigators will determine whether HTLV-II infection predisposes to bacterial pneumonia by creating immune dysfunction in these cells which are known to be critical for natural protection against pneumococcal pneumonia, the most common cause of bacterial pneumonia in individuals with immune dysfunction. Studies planned for the next five years address the immune status of HTLV-II-infected persons. HTLV-II-infected and -uninfected individuals will be vaccinated with the pneumococcal 23-valent polysaccharide vaccine, and their qualitative and quantitative antibody responses will be investigated by determining the isotype and IgG subclass distribution, concentration, avidity and opsonic function of specific pneumococcal capsular antibodies. The same individuals will also be vaccinated with tetanus toxoid protein antigen as a control for antibody response to a separate class of antigen, and their antibody responses measured. The effect of HTLV-II infection of T cells on the proliferative and antibody-secreting functions of B lymphocytes will be tested. CD4+ and CD8+ T cells will be isolated from HTLV-II-infected persons using immunobeads, co-cultivated with normal B lymphocytes, and the functional activity of the B cells assessed using mitogen stimulation and ELISA antibody quantitation assays. Levels of B cell regulatory cytokines produced by infected and uninfected T cells will be measured by ELISA. Levels of immune response markers IL2 receptor on CD8+ T cells, and CD21 and CD35 on B cells will be determined by flow cytometry. The phagocytic and bactericidal function of PMN and of human macrophages derived from the monocytes from HTLV-II-infected individuals will be tested and compared to the function of those cells from uninfected persons. Human CD4+ and CD8+ T cells will be isolated using immunobeads and quantities of macrophage and PMN regulatory cytokines produced by HTLV-II-infected and -uninfected T Cells will be measured by ELISA. The effect of HTLV-II infection of human T cells on cytokine-dependent activation of macrophages and PMN will be studied using functional assays of pneumococcal phagocytic killing.

描述（改编自申请人的摘要）：该项目旨在 了解流行病学结果观察的免疫学基础 HTLV-II 感染的献血者细菌性肺炎的发病率增加。 在一项针对 HTLV-II 血清阳性且静脉注射药物的人的研究中 与患有细菌性肺炎的患者相比，使用该药物会增加细菌性肺炎的风险 没有发现任何风险。细菌感染风险增加的类似发现 在临床结果中观察到 HTLV-II 感染者出现肺炎 参与逆转录病毒流行病学研究的献血者分析 捐助者研究。由于HTLV-II感染的细胞趋向性包括CD4+和 CD8+ T 细胞、B 细胞和单核细胞，研究人员将确定是否 HTLV-II 感染通过产生免疫而诱发细菌性肺炎 这些细胞的功能障碍已知对自然生命至关重要 预防肺炎球菌肺炎，这是细菌性肺炎最常见的原因 患有免疫功能障碍的人会患上肺炎。 计划在未来五年进行的研究涉及免疫状态 HTLV-II 感染者。 HTLV-II 感染者和未感染者将 接种肺炎球菌23价多糖疫苗后， 定性和定量抗体反应将通过以下方式进行研究 确定同种型和 IgG 亚类分布、浓度、亲合力 和特定肺炎球菌荚膜抗体的调理功能。相同 个人还将接种破伤风类毒素蛋白抗原作为 控制抗体对一类单独抗原的反应，及其 测量抗体反应。 HTLV-II感染T细胞对T细胞的影响 将测试B淋巴细胞的增殖和抗体分泌功能。 使用以下方法从 HTLV-II 感染者中分离 CD4+ 和 CD8+ T 细胞 与正常 B 淋巴细胞共培养的免疫珠，以及功能性的 使用丝裂原刺激和 ELISA 抗体评估 B 细胞的活性 定量分析。感染者产生的 B 细胞调节细胞因子水平 未感染的T细胞将通过ELISA进行测量。免疫反应水平 CD8+ T 细胞上的 IL2 受体标记物以及 B 细胞上的 CD21 和 CD35 标记物将 通过流式细胞术测定。 PMN的吞噬和杀菌功能 以及源自 HTLV-II 感染的单核细胞的人巨噬细胞 将对个体进行测试并与来自这些细胞的功能进行比较 未感染者。将使用以下方法分离人类 CD4+ 和 CD8+ T 细胞 产生的免疫珠以及巨噬细胞和 PMN 调节细胞因子的数量 将通过 ELISA 测量 HTLV-II 感染和未感染的 T 细胞。这 HTLV-II感染人类T细胞对细胞因子依赖性激活的影响 将使用肺炎球菌的功能测定来研究巨噬细胞和中性粒细胞的功能 吞噬杀戮。