Wipasa Jiraprapa, Wongkulab Panuwat, Chawansuntati Kriangkrai, Chaiwarit Romanee, Supparatpinyo Khuanchai
Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.
Department of Medicine, Chiang Mai University, Chiang Mai, Thailand.
PLoS One. 2014 Oct 20;9(10):e110276. doi: 10.1371/journal.pone.0110276. eCollection 2014.
Cell-mediated immunity plays a crucial role in resistance to intracellular infection. We previously reported antibodies against interferon-gamma (IFN-γ) in HIV- negative (HIV-) patients with acquired immunodeficiency presenting with repeated episodes of disseminated infection caused by uncommon opportunistic intracellular fungal, bacterial, and viral pathogens. This follow-up study aimed to investigate cellular immune responses in these unusual patients.
Twenty HIV- patients presenting with ≥2 episodes of culture- or histopathologic-proven opportunistic infections were enrolled along with age- and sex-matched controls comprised of 20 HIV+ patients plus 20 healthy adults. Monocyte phenotyping and intracellular cytokine production were determined by staining with specific antibodies followed by flow cytometry. Anti-interferon-γ antibodies were measured by enzyme-linked immunosorbent assay, and inducible nitric oxide synthase by reverse-transcription polymerase chain reaction.
There were no differences among cases, HIV+, and healthy controls in the percentage of monocytes, or CD68 and HLA-DR expression on their surfaces. FcR1 (CD119) expression on monocytes was significantly higher in cases than in HIV+ (p<0.05) and healthy controls (p<0.01), suggesting the presence of activated monocytes in the circulation. Interleukin (IL)-2 and tumor necrosis factor (TNF)-α production in CD4 cells were significantly lower in cases than in healthy controls (p<0.01 and p<0.001, respectively). CD8 production of TNF-α among cases was significantly lower than that of healthy controls (p<0.05).
Immunodeficiency in HIV- individuals with repeated infections with intracellular pathogens may be associated with one or more of the abnormal immune responses reflected by the reduced production of both IL-2 by CD4 T cells and TNF-α by CD4 T cells and CD8 T cells, as well as presence of anti-IFN-γ antibody, as previously reported.
细胞介导的免疫在抵抗细胞内感染中起关键作用。我们之前报道了在获得性免疫缺陷的HIV阴性（HIV-）患者中存在抗干扰素-γ（IFN-γ）抗体，这些患者反复出现由不常见的机会性细胞内真菌、细菌和病毒病原体引起的播散性感染。这项随访研究旨在调查这些特殊患者的细胞免疫反应。
招募了20例有≥2次经培养或组织病理学证实的机会性感染的HIV-患者，以及年龄和性别匹配的对照组，包括20例HIV+患者和20名健康成年人。通过用特异性抗体染色后进行流式细胞术来确定单核细胞表型和细胞内细胞因子的产生。通过酶联免疫吸附测定法测量抗干扰素-γ抗体，通过逆转录聚合酶链反应测量诱导型一氧化氮合酶。
病例组、HIV+组和健康对照组在单核细胞百分比或其表面CD68和HLA-DR表达方面没有差异。病例组单核细胞上FcR1（CD119）的表达显著高于HIV+组（p<0.05）和健康对照组（p<0.01），表明循环中存在活化的单核细胞。病例组CD4细胞中白细胞介素（IL）-2和肿瘤坏死因子（TNF）-α的产生显著低于健康对照组（分别为p<0.01和p<0.001）。病例组中CD8细胞产生的TNF-α显著低于健康对照组（p<0.05）。
如先前报道，反复感染细胞内病原体的HIV-个体的免疫缺陷可能与以下一种或多种异常免疫反应有关：CD4 T细胞产生IL-2减少、CD4 T细胞和CD8 T细胞产生TNF-α减少以及存在抗IFN-γ抗体。
