CELLULAR IMMUNE FUNCTION IN AIDS AND IN PRIMARY IMMUNE DEFICIENCIES

艾滋病和原发性免疫缺陷中的细胞免疫功能

• 批准号: 3808600
• 负责人: G M SHEARER
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3808600
• 关键词: 2'3' dideoxynucleoside; AIDS; AIDS vaccines; CD4 molecule; CD8 molecule; HIV infections; MHC class II antigen; T lymphocyte; active immunization; adult human (21+); antiAIDS agent; antigen presenting cell; antigens; cell mediated lymphocytolysis test; cellular immunity; child (0-11); helper T lymphocyte; human subject; human tissue; immunoglobulin G; interleukin 2; polymerase chain reaction; serotyping; zidovudine

Peripheral blood leukocytes (PBL) from AIDS patients but not from asymptomatic HIV-infected (HIV+) individuals exhibit two distinct types of antigen presenting cell (APC) defects. PBL from children infected with HIV exhibit the same complex spectrum of T helper cell (Th) defects that we reported in adult patients. PBL from healthy HIV- children do not generate Th responses to recall until 2 years of age, although T cell responses to HLA alloantigens (ALLO) and phytohemagglutinin (PHA) are strong at birth. The early defect in Th responses to recall antigens seen in HIV+ adults and children is associated with a non-HIV inhibitory factor that is produced by CD8+ cells and is selective in its action in that it only suppresses HLA self-restricted Th responses. PBL from volunteers immunized with a candidate AIDS vaccine generate potent HIV-specific T helper and effector responses, even one year after immunization. Using our in vitro Th tests, we can detect long-term improvement in Th function in more than 50% of patients on AZT, ddI, or soluble CD4-IgG therapy. We can detect evidence of HIV exposure by sensitive HIV-specific T cell tests, using PBL from high risk HIV seronegative cohorts who are also HIV- by the polymerase chain reaction. Studies of patients with primary immune deficiencies exhibit defects in Th and APC function. Patients with Wiskott-Aldrich Syndrome exhibit a defect that involves an unstable immunogenic complex that is formed by self HLA class I, beta2-microglobulin and antigenic peptide.

艾滋病患者的外周血白细胞（PBL），但不是 无症状的HIV感染（HIV+）个体表现出两种不同的类型 抗原呈现细胞（APC）缺陷的缺陷。 感染儿童的PBL HIV表现出相同的T辅助细胞（Th）缺陷的复杂频谱 我们在成年患者中报告的。 健康的艾滋病毒的PBL-儿童确实 尽管T细胞，直到2岁时才产生对回忆的反应 对HLA同种抗原（Allo）和植物凝集素（PHA）的反应是 出生时强壮。 回忆抗原的反应的早期缺陷 在艾滋病毒+成人和儿童中可见与非HIV抑制作用有关 CD8+细胞产生的因素，其作用具有选择性 它只会抑制HLA自由的TH反应。 来自 用候选艾滋病疫苗免疫的志愿者会产生有效 甚至一年后 免疫。 使用我们的体外测试，我们可以检测到长期 在AZT，DDI或 可溶性CD4-IGG治疗。 我们可以检测到通过 使用来自高风险HIV的PBL，对HIV特异性T细胞测试进行了敏感的HIV特异性T细胞测试 血清神经群也是HIV-聚合酶链反应。 对原发性免疫缺陷患者的研究表现出缺陷 在TH和APC功能中。 Wiskott-Aldrich综合征患者表现出A 涉及不稳定的免疫原性复合物的缺陷 自我HLA I类，beta2-微球蛋白和抗原肽。