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Specific Pathogen-Free Status Alters Immunophenotype in Rhesus Macaques: Implications for the Study of Simian Immunodeficiency Virus

机译:特定的无病原状态改变猕猴的免疫表型:猿猴免疫缺陷病毒研究的意义。

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摘要

The repertoire of viruses to which research primates are exposed, even in the absence of clinical disease, may contribute to experimental confounding. In this study we examined whether standard specific pathogen-free (SPF) rhesus macaques exposed to a wider spectrum of enzootic viruses and expanded SPF macaques derived to exclude a greater number of viral agents would display alterations in immune activation or immune cell populations. Given the impact of immunophenotype on human immunodeficiency virus (HIV) progression and the importance of the simian immunodeficiency virus (SIV) model for the study of HIV pathogenesis, we elected to additionally examine the impact of SPF status on the capacity of peripheral blood mononuclear cells (PBMCs) to support SIV replication. The expanded SPF group displayed significant immune alterations including increased serum interleukin (IL)-15 and a greater in vitro elaboration of GM-CSF, IL1ra, VEGF, IL-10, IL12/23, and MIP-1b. Consistent with reduced viral antigenic exposure in expanded SPF macaques, decreased CD4+ and CD8+ transitional and effector memory (TEM) cell populations were observed. Expanded SPF PBMC cultures also demonstrated an increased peak (192.61 ng/ml p27) and area under the curve in in vitro SIV production (1968.64 ng/ml p27) when compared to standard SPF macaques (99.32 ng/ml p27; p=0.03 and 915.17 ng/ml p27; p=0.03, respectively). In vitro SIV replication did not correlate with CD4+ TEM cell counts but was highly correlated with serum IL-15 in the subset of animals examined. Findings suggest that an altered immunophenotype associated with the maintenance of primates under differing levels of bioexclusion has the potential to impact the outcome of SIV studies and models for which the measurement of immunologic endpoints is critical.
机译:即使在没有临床疾病的情况下,研究灵长类动物所接触的病毒库也可能导致实验混乱。在这项研究中,我们研究了暴露于更广泛的动物病毒中的标准无特定病原体(SPF)恒河猴和衍生以排除更多病毒制剂的扩展SPF猕猴是否会在免疫激活或免疫细胞群中显示出变化。考虑到免疫表型对人类免疫缺陷病毒(HIV)进程的影响以及猿猴免疫缺陷病毒(SIV)模型在研究HIV发病机理中的重要性,我们选择另外检查SPF状况对外周血单核细胞能力的影响(PBMC)以支持SIV复制。扩展的SPF组显示出明显的免疫改变,包括血清白介素(IL)-15升高以及GM-CSF,IL1ra,VEGF,IL-10,IL12 / 23和MIP-1b的体外修饰作用增强。与扩大的SPF猕猴的病毒抗原暴露减少一致,观察到CD4 + 和CD8 + 过渡和效应记忆(TEM)细胞群体减少。与标准SPF猕猴(99.32ngng / ml p27; p = 0.03和p = 0.03)相比,扩展的SPF PBMC培养物在体外SIV产生时的峰下(192.61 ng / ml p27)和曲线下面积也有所增加(1968.64 ng / ml p27)。 915.17 ng / ml p27; p = 0.03)。体外SIV复制与CD4 + TEM细胞计数无关,但与所检查动物亚群中的血清IL-15高度相关。研究结果表明,在不同的生物排斥水平下,与灵长类动物维持相关的改变的免疫表型可能会影响SIV研究和模型的结果,因此对于免疫学终点的测量至关重要。

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