Interferon-γ-mediated pathways and in vitro PBMC proliferation in HIV-infected patients
Interferon-γ-mediated pathways and in vitro PBMC proliferation in HIV-infected patients
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DOI：
10.1515/bc.2009.018
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发表时间：
2009-02-01
影响因子：
3.7
通讯作者：
Zangerle, Robert
中科院分区：
文献类型：
--
作者：
Schroecksnadel, Katharina;Winkler, Christiana;Zangerle, Robert
HIV感染的特征是进行性免疫缺陷：感染HIV的外周血单核细胞(PBMC)不能对同种抗原和有丝分裂原刺激做出正确反应。在这项研究中，我们在体外检测了干扰素-γ(干扰素-γ)介导的途径和丝裂原刺激的HIV感染的PBMCs的增殖反应。用有丝分裂原刀豆蛋白A(ConA)、植物血凝素(PHA)和商陆有丝分裂原(PWM)刺激30例HIV感染者的PBMC。有丝分裂原刺激诱导HIV感染和对照PBMC表达干扰素-γ、GTP环水解酶I(GCH-I)和吲哚胺(2，3)双加氧酶(IDO)，促进新蝶呤的形成和色氨酸的降解。干扰素-γ浓度与新喋呤水平和色氨酸降解率相关。HIV患者对PHA和PWM细胞因子的增殖反应较低，干扰素-γ的形成预示着增殖反应。感染HIV的PBMCs在感染6h后，干扰素-γ、GCH-I和IDO的高表达与其较好的增殖反应有关。综上所述，干扰素-γ及后续酶的诱导似乎在体外对HIV感染的PBMC的增殖反应有重要影响，提示细胞因子在免疫缺陷的发生发展中起着突出的作用。
HIV infection is characterized by progressive immunodeficiency: HIV-infected peripheral blood mononuclear cells (PBMCs) cannot properly react to stimulation with allo-antigens and mitogens. In this study, we examined interferon-gamma (IFN-gamma)-mediated pathways and the proliferative response of mitogen-stimulated HIV-infected PBMCs in vitro. PBMCs of 30 HIV-infected patients were stimulated with the mitogens concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM). Mitogen stimulation induced expression of IFN-gamma, GTP cyclohydrolase I (GCH-I), and indoleamine (2,3)dioxygenase (IDO) resulting in enhanced neopterin formation and tryptophan degradation by HIV-infected and control PBMCs. IFN-gamma concentrations correlated with neopterin levels and tryptophan degradation. Proliferative responses to PHA and PWM cytokine were lower in HIV patients, with IFN-gamma formation predicting proliferative responses. Higher mRNA expression of IFN-gamma, GCH-I and IDO after 6 h was related to better proliferative responses in HIV-infected PBMCs. In conclusion, induction of IFN-gamma and subsequent enzymes appears to importantly influence the proliferative response of HIV-infected PBMCs in vitro, suggesting a prominent role of the cytokine in the development of immunodeficiency.