T cell activation, apoptosis and cytokine dysregulation in the (co)pathogenesis of HIV and pulmonary tuberculosis (TB)

T cell activation, apoptosis and cytokine dysregulation in the (co)pathogenesis of HIV and pulmonary tuberculosis (TB)
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DOI:
10.1046/j.1365-2249.2000.01385.x
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发表时间:
2000-12-01
影响因子:
4.6
通讯作者:
Vanham, G
Vanham, G
中科院分区:
医学3区
文献类型:
--
作者:
Hertoghe, T;Wajja, A;Vanham, G

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比较了4组乌干达受试者:HIV(-)和HIV+成人活动性肺结核患者(HIV-PTB n=38;HIV+PTB n=28)、单纯HIV感染者(n=26)和PPD+健康对照组(n=25)的免疫参数。与健康对照组相比,HIV和/或PTB患者外周血中的CD4、CD8T细胞表达更多的活化标志(HLA-DR、CD38),CD8T细胞表达更多的CD95(凋亡前)和更少的CD28(共刺激受体)。人类免疫缺陷病毒(HIV)和肺结核患者外周血单个核细胞(PBMC)在抗原刺激下产生干扰素-γ(干扰素-γ)受损。以单核细胞增多、粒细胞增多、转化生长因子-β1生成增加和PPD诱导的细胞凋亡为特征的PTB(无论有无HIV)。在体内,CD4T细胞耗尽,体外自发的CD4T细胞凋亡增加,以及在有丝分裂刺激下干扰素-γ反应的缺陷仅限于HIV+受试者(有或没有PTB)。与肺结核和艾滋病毒相关的重叠和独特的免疫变化可能解释了这两种疾病相互不利的影响。
Immune parameters were compared in four groups of Ugandan subjects: HIV(-)and HIV+ adult patients with active pulmonary TB (HIV- PTB n = 38; HIV+ PTB n = 28), patients with HIV infection only (n = 26) and PPD+ healthy controls (n = 25). Compared with healthy controls, CD4 and CD8 T cells from patients with HIV and/or PTB expressed more activation markers (HLA-DR, CD38); their CD8 T cells expressed more CD95 (pre-apoptosis) and less CD28 (co-stimulatory receptor). Peripheral blood mononuclear cells (PBMC) of patients with either HIV or PTB were impaired in interferon-gamma (IFN-gamma) production upon antigenic stimulation. PTB (with or without HIV) was characterized by monocytosis, granulocytosis, increased transforming growth factor-beta 1 production and PPD-induced apoptosis. In vivo CD4 T cell depletion, in vitro increased spontaneous CD4 T cell apoptosis and defects in IFN-gamma responses upon mitogenic stimulation were restricted to HIV+ subjects (with or without PTB). Overlapping and distinctive immune alterations, associated with PTB and HIV, might explain mutual unfavourable influences of both diseases.