CELLULAR IMMUNE FUNCTION IN AIDS AND CANCER

免疫调节细胞因子的变化是由HIV感染引起的， 减少1型细胞因子，增强细胞免疫(CI)和 增加2型细胞因子，增强体液免疫(HI)。IL-12和 IL-10分别增强CI和HI，并由 单核/巨噬细胞(M/M)，HIV感染的重要靶点。男/女 从HIV+患者产生的IL-12水平降低和水平上升 IL-10的表达，以及体外感染HIV的M/M的表达。IL-12 p40和p35基因的表达 在晚期患者中表达降低，但在无症状患者中不表达。 艾滋病病毒蛋白水解酶治疗儿童艾滋病的临床研究 抑制剂表明，出现病毒减少的患者 负荷和CD4计数的增加没有表现出正常的IL-12和IL-12- 10生产。这一发现表明，蛋白酶抑制剂诱导了 CD4计数和病毒载量的变化不会反映在免疫功能的改善上 功能。来自HIV感染母亲的未感染新生儿的M/M不 产生IL-12，与未感染艾滋病毒的新生儿的M/M相反 产生IL-12的母亲。HIV诱导的细胞因子失调可能 是由于减少了信号转换器和激活器 转录(STATS)，作为来自HIV感染患者的T细胞以及 在体外感染HIV-1的T细胞显示STAT5水平降低， 但不是其他已知的统计数据。血清阴性，HIV暴露，T细胞- 有反应的个体在以下情况下表现出显性的1型细胞因子 被HIV抗原刺激，而HIV感染者表现出 一种主要的2型细胞因子模式。人类白细胞抗原诱导的CD8+T细胞株 同种异体抗原混合淋巴细胞刺激产生一种阻断 HIV感染PHA刺激自体和同种异体靶点，以及 对人成纤维细胞系CMV感染也有抑制作用。这 同种异体抗原刺激的CD8抗病毒因子似乎没有任何 B-趋化因子。该因子抑制T向、M向和 HIV-1的初级分离株，以及一个慢性感染的细胞系。 因此，这种异体刺激因子在体外能够阻断 多个艾滋病毒分离株，以及一种机会性病毒 对艾滋病来说是有问题的。AZT被掺入胎儿脐带血中 大多数在怀孕期间接受AZT治疗的妇女的白细胞。 基于小鼠模型的经验，这一发现提高了 长期AZT诱发子代致癌的可能性。 艾滋病标题：艾滋病毒/艾滋病中的免疫缺陷。

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.