IMMUNOLOGY OF BACTERIAL PNEUMONIA IN HTLV-II INFECTION

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， 在HTLV-II感染的献血者中细菌性肺炎的发病率增加。 在一项对HTLV-II血清阳性和静脉注射药物的人进行的研究中， 使用，与使用抗生素的患者相比， 这两种风险都没有被发现。一个类似的发现， 在临床结果中观察到HTLV-II感染个体的肺炎 参加逆转录病毒流行病学调查的献血者分析 供体研究。由于HTLV-II感染的细胞嗜性包括CD 4+和CD 4 + T细胞， CD 8 + T细胞、B细胞和单核细胞，研究者将确定是否 HTLV-II感染易患细菌性肺炎， 这些细胞中的功能障碍，已知对自然 预防肺炎球菌肺炎，最常见的细菌性肺炎 免疫功能紊乱的人的肺炎。 计划在未来五年内开展的研究将解决以下问题： HTLV-II感染者。HTLV-II感染和未感染的个体将被 接种肺炎球菌23价多糖疫苗， 定性和定量抗体应答将通过以下方法进行研究： 确定同种型和IgG亚类分布、浓度、亲合力 和特异性肺炎球菌荚膜抗体的调理功能。相同的 个人也将接种破伤风类毒素蛋白抗原作为 针对单独一类抗原的抗体应答的对照，以及它们的 测量抗体应答。HTLV-II感染T细胞对T细胞增殖的影响 将测试B淋巴细胞的增殖和抗体分泌功能。 将使用以下方法从HTLV-II感染者中分离CD 4+和CD 8 + T细胞： 与正常B淋巴细胞共培养， 使用有丝分裂原刺激和ELISA抗体评估B细胞的活性 定量分析。受感染细胞产生的B细胞调节细胞因子水平 而未感染的T细胞将通过ELISA测量。免疫反应水平 CD 8 + T细胞上的标志物IL 2受体，以及B细胞上的CD 21和CD 35将被 通过流式细胞术测定。中性粒细胞的吞噬和杀菌功能 和来自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 未感染的人。人CD 4+和CD 8 + T细胞将使用 免疫球蛋白和巨噬细胞和PMN调节细胞因子的产生量 通过ELISA测量HTLV-II感染的和未感染的T细胞。的 HTLV-II感染人T细胞对嘌呤依赖性活化作用 巨噬细胞和中性粒细胞将使用肺炎球菌的功能测定进行研究， 吞噬杀伤

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.