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首页> 外文期刊>Clinical and diagnostic laboratory immunology >Differential effect of the immunomodulatory hormone somatostatin on replication of human immunodeficiency virus type 1 in CD4+ and CD8+ T lymphocytes.
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Differential effect of the immunomodulatory hormone somatostatin on replication of human immunodeficiency virus type 1 in CD4+ and CD8+ T lymphocytes.

机译:免疫调节激素生长抑素对CD4 +和CD8 + T淋巴细胞中1型人类免疫缺陷病毒复制的影响。

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The long-acting somatostatin analog octreotide (SMS 201-995) possesses immunosuppressive properties and has been successfully used for the management of human immunodeficiency virus (HIV)-associated diarrhea, a condition commonly observed in the absence of known enteric pathogens. Since HIV type 1 (HIV-1) replication can occur in both CD4+ and CD8+ lymphocytes, we hypothesized that this benefit might be due to local effects on HIV-1 replication in these two T-cell subsets. As a model, we studied the effects of two synthetic molecules, SRIH 1-14 and SRIH 1-28, closely related to naturally occurring forms of somatostatin, as well as SMS 201-995 on HIV-1 replication in CD4+ and CD8+ cells derived from peripheral blood mononuclear cells (PBMC). We found that HIV-1 replication was inhibited in CD8+ cells but enhanced in infected CD4+ lymphocytes, as measured by p24 antigen levels in culture fluids. These differential effects were drug concentration dependent. We also observed that somatostatin inhibited the mitogen-induced proliferative responsiveness of both cell types. These effects on both HIV-1 replication and cell proliferation were independent of somatostatin gene expression, since somatostatin mRNAs were not detected in mitogen-stimulated PBMC, as determined by reverse transcription-PCR.
机译:长效生长抑素类似物奥曲肽(SMS 201-995)具有免疫抑制特性,已成功用于人免疫缺陷病毒(HIV)相关性腹泻的治疗,这种情况通常在没有已知肠病原体的情况下观察到。由于HIV 1型(HIV-1)复制可同时在CD4 +和CD8 +淋巴细胞中发生,因此我们假设这种益处可能是由于这两个T细胞亚群中对HIV-1复制的局部影响。作为模型,我们研究了两种合成分子SRIH 1-14和SRIH 1-28(与生长抑素的天然存在形式密切相关)以及SMS 201-995对CD4 +和CD8 +细胞中HIV-1复制的影响来自外周血单核细胞(PBMC)。我们发现,HIV-1复制在CD8 +细胞中受到抑制,但在受感染的CD4 +淋巴细胞中得到增强,如培养液中p24抗原水平所衡量。这些差异作用取决于药物浓度。我们还观察到生长抑素抑制了两种细胞类型的丝裂原诱导的增殖反应。这些对HIV-1复制和细胞增殖的影响均不受生长抑素基因表达的影响,因为在有丝分裂原刺激的PBMC中未检测到生长抑素mRNA(通过逆转录PCR进行检测)。

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