CELLULAR IMMUNE FUNCTION IN AIDS AND CANCER

艾滋病和癌症中的细胞免疫功能

• 批准号: 6100958
• 负责人: G M SHEARER
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 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/6100958
• 关键词: AIDS; AIDS vaccines; HIV infections; Wiskott Aldrich syndrome; cellular immunity; cytokine; disease /disorder proneness /risk; helper T lymphocyte; human subject; humoral immunity; immunogenetics; influenza vaccines; longitudinal human study; pediatric AIDS; prognosis; serotyping; tissue /cell culture; virus DNA; virus antigen; virus load

Immunoregulatory cytokine changes result from HIV infection, with decreased type 1 cytokines that enhance cellular immunity (CI) and increased type 2 cytokines that augment humoral immunity (HI). IL-12 and IL-10 enhance CI and HI, respectively, and are produced by monocytes/macrophages (M/M), important targets of HIV infection. M/M from HIV+ patients produced reduced levels of IL-12 and increased levels of IL-10, as did M/M infected in vitro with HIV. IL-12 p40 and p35 mRNA expression was reduced in advanced but not in asymptomatic patients. Therapeutic trials of pediatric AIDS patients with HIV protease inhibitors suggested that patients who presented with reduced viral loads and increased CD4 counts did not exhibit normalized IL-12 and IL- 10 production. This finding suggests that protease inhibitor-induced changes in CD4 count and viral load is not reflected in improved immune function. M/M from uninfected newborns of HIV-infected mothers do not produce IL-12, in contrast to the M/M of newborns of HIV uninfected mothers that do produce IL-12. HIV-induced cytokine dysregulation may be due to a reduction in signal transducers and activators of transcription (STATs), as T cells from HIV-infected patients as well as T cells infected in vitro with HIV-1 exhibited reduced levels of STAT5, but not of the other known STATs. Seronegative, HIV-exposed, T cell- responsive individuals exhibited a dominant type 1 cytokine profile when stimulated with HIV antigens, whereas HIV-infected individuals showed a dominant type 2 cytokine pattern. CD8+ T cell lines resulting from HLA alloantigen mixed lymphocyte stimulation generated a factor that blocked HIV infection of PHA stimulated autologous and allogeneic targets, and also inhibited CMV infection of human fibroblast cell lines. This alloantigen stimulated CD8 anti-viral factor does not appear to be any of the b-chemokines. The factor inhibited T-tropic, M-tropic, and primary isolates of HIV-1, as well as a chronically- infected cell line. Thus, this allo-stimulated factor is capable in vitro of blocking multiple HIV isolates, as well as one of the opportunistic viruses that is problematic in AIDS. AZT was incorporated into the fetal cord blood leukocytes from a majority of women who received AZT during pregnancy. Based on experience from a murine model, this finding raises the possibility of long-term AZT-induced carcinogenesis in the offspring. AIDS title: Immune Defects in HIV/AIDS.

免疫调节细胞因子的变化是由HIV感染引起的， 降低1型细胞因子，增强细胞免疫（CI）和 增加了增强体液免疫（HI）的2型细胞因子。 IL-12和 IL-10分别增强了CI和HI，由 单核细胞/巨噬细胞（M/M），HIV感染的重要靶标。毫米 来自HIV+患者的IL-12水平降低，水平降低 IL-10的M/M和HIV体外感染的M/M也是如此。 IL-12 P40和P35 mRNA 在无症状患者中，在晚期但没有降低表达。 小儿艾滋病HIV蛋白酶患者的治疗试验 抑制剂表明，病毒降低的患者 负载和CD4计数增加未表现出标准化的IL-12和IL- 10生产。这一发现表明蛋白酶抑制剂诱导 CD4计数和病毒负荷的变化不反映在改善的免疫力中 功能。来自未感染的艾滋病毒感染母亲的新生儿的m/m没有 与未感染的艾滋病毒新生儿的m/m产生IL-12 确实会产生IL-12的母亲。 HIV诱导的细胞因子失调可能 由于信号传感器和激活因素的减少 转录（Stats），作为来自HIV感染患者的T细胞以及 HIV-1体外感染的T细胞表现出降低的STAT5水平 但不是其他已知统计数据。血清调，艾滋病毒暴露，T细胞 - 反应敏感的个体在 用艾滋病毒抗原刺激，而艾滋病毒感染的个体显示 主要的2型细胞因子模式。由HLA产生的CD8+ T细胞系 同种抗原混合淋巴细胞刺激产生了阻塞的因素 PHA的HIV感染刺激自体和同种异体靶标，以及 还抑制了人成纤维细胞细胞系的CMV感染。这 同种抗原刺激CD8抗病毒因子似乎没有任何 b-phemokines。该因子抑制了T-热带，M-热带和 HIV-1的主要分离株以及长期感染的细胞系。 因此，这个同种刺激的因子能够在封闭的体外体外 多种艾滋病毒分离株以及一种机会性病毒之一 在艾滋病中是有问题的。将AZT纳入胎儿血液中 怀孕期间接受AZT的大多数妇女的白细胞。 根据鼠模型的经验，这一发现提高了 在后代中长期诱导的癌变的可能性。 艾滋病标题：艾滋病毒/艾滋病中的免疫缺陷。