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首页> 外文期刊>Clinical and diagnostic laboratory immunology >Differential effects of interleukin-12, interleukin-15, and interleukin-2 on human immunodeficiency virus type 1 replication in vitro.
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Differential effects of interleukin-12, interleukin-15, and interleukin-2 on human immunodeficiency virus type 1 replication in vitro.

机译:白细胞介素12,白细胞介素15和白细胞介素2对人免疫缺陷病毒1型体外复制的差异作用。

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Cytokines may have clinical utility as therapeutic agents for human immunodeficiency virus type 1 (HIV-1) infection and as an adjuvant for vaccines. The effect of interleukin-12 (IL-12) and IL-15 on in vitro HIV-1 replication was investigated. IL-12 and IL-15 at doses up to 10 ng/ml had little effect on basal HIV-1 p24 antigen production by chronically HIV-infected T (ACH-2) and monocytic (U1) cell lines. For ACH-2 cells stimulated with phorbol 12-myristate 13-acetate (PMA; 50 ng/ml), IL-12 and IL-15 significantly increased p24 antigen production by 20 and 30%, respectively (n = 6). In contrast, IL-12 and IL-15 (10 ng/ml) treatment of PMA-stimulated U1 cells decreased p24 antigen production by 16 and 15%, respectively (n = 6). We next studied the effect of IL-12 and IL-15 on HIV-infected peripheral blood mononuclear cells (PBMCs). In 10 HIV-seropositive patients' PBMCs cocultured with mitogen-activated HIV-seronegative donor cells, two patterns of p24 antigen production were observed in response to IL-2: low (p24 antigen production < 10(3) pg/ml; n = 8) and high (p24 antigen production > 10(3) pg/ml; n = 2) response. For the low-response pattern, IL-12 and IL-15 increased viral replication by 97-fold and 100-fold, respectively (P = 0.05 and 0.004, respectively). For the high-response pattern, both IL-12 and IL-15 suppressed HIV replication. The effect of IL-2, IL-12, and IL-15 on acute in vitro infection by HIV-1JRCSF was also examined. IL-12 did not increase p24 antigen production above basal levels while IL-2 and IL-15 significantly enhanced p24 antigen production (by approximately 2-fold). In conclusion, IL-12 and IL-15 may have differential effects on latent and acute HIV infection, and their ability to enhance HIV production may depend on cell activation. Thus, the use of these cytokines may be dictated by the clinical state of the patient.
机译:细胞因子可以作为人类1型免疫缺陷病毒(HIV-1)感染的治疗剂和疫苗佐剂具有临床用途。研究了白介素12(IL-12)和IL-15对体外HIV-1复制的影响。最高10 ng / ml的IL-12和IL-15对慢性HIV感染的T(ACH-2)和单核细胞(U1)细胞系对基础HIV-1 p24抗原产生的影响很小。对于佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA; 50 ng / ml)刺激的ACH-2细胞,IL-12和IL-15分别显着提高了p24抗原产生20%和30%(n = 6)。相反,对PMA刺激的U1细胞进行IL-12和IL-15(10 ng / ml)处理后,p24抗原的产生分别降低了16%和15%(n = 6)。接下来,我们研究了IL-12和IL-15对HIV感染的外周血单核细胞(PBMC)的影响。在10个HIV血清反应阳性患者的PBMC中,与促分裂原激活的HIV血清阴性供体细胞共培养,观察到IL-2有两种模式的p24抗原产生:低(p24抗原产生<10(3)pg / ml; n = 8)和高(p24抗原产生> 10(3)pg / ml; n = 2)反应。对于低响应模式,IL-12和IL-15分别使病毒复制增加了97倍和100倍(分别为P = 0.05和0.004)。对于高应答模式,IL-12和IL-15均抑制HIV复制。还检查了IL-2,IL-12和IL-15对HIV-1JRCSF急性体外感染的影响。 IL-12不会将p24抗原的产生增加到高于基础水平,而IL-2和IL-15则显着提高了p24抗原的产生(大约2倍)。总之,IL-12和IL-15对潜在和急性HIV感染可能具有不同的作用,它们增强HIV产生的能力可能取决于细胞活化。因此,这些细胞因子的使用可以由患者的临床状态决定。

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