首页> 外文OA文献 >Inhibition of acute in vivo human immunodeficiency virus infection by human interleukin 10 treatment of SCID mice implanted with human fetal thymus and liver.
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Inhibition of acute in vivo human immunodeficiency virus infection by human interleukin 10 treatment of SCID mice implanted with human fetal thymus and liver.

机译:人白介素10处理植入人胎胸腺和肝脏的SCID小鼠对急性体内人免疫缺陷病毒感染的抑制作用。

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摘要

To improve the usefulness of in vivo mode for the investigation of the pathophysiology of human immunodeficiency virus (HIV) infection, we modified the construction of SCID mice implanted with human fetal thymus and liver (thy/liv-SCID-hu mice) so that the peripheral blood of the mice contained significant numbers of human monocytes and T cells. After inoculation with HIV-1(59), a primary patient isolate capable of infecting monocytes and T cells, the modified thy/liv-SCID-hu mice developed disseminated HIV infection that was associated with plasma viremia. The development of plasma viremia and HIV infection in thy/liv-SCID-hu mice inoculated with HIV-1(59) was inhibited by acute treatment with human interleukin (IL) 10 but not with human IL-12. The human peripheral blood mononuclear cells in these modified thy/liv-SCID-hu mice were responsive to in vivo treatment with exogenous cytokines. Human interferon gamma expression in the circulating human peripheral blood mononuclear cells was induced by treatment with IL-12 and inhibited by treatment with IL-10. Thus, these modified thy/liv-SCID-hu mice should prove to be a valuable in vivo model for examining the role of immunomodulatory therapy in modifying HIV infection. Furthermore, our demonstration of the vivo inhibitory effect of IL-10 on acute HIV infection suggests that further studies may be warranted to evaluate whether there is a role for IL-10 therapy in preventing HIV infection in individuals soon after exposure to HIV such as for children born to HIV-infected mothers.
机译:为了提高体内模式对人类免疫缺陷病毒(HIV)感染的病理生理学调查的有用性,我们修改了植入人胎儿胸腺和肝脏的SCID小鼠(thy / liv-SCID-hu小鼠)的结构。小鼠的外周血中含有大量的人单核细胞和T细胞。接种了HIV-1(59)(一种能够感染单核细胞和T细胞的主要患者隔离株)后,经过修饰的thy / liv-SCID-hu小鼠发生了传播性HIV感染,这与血浆病毒血症有关。用人白介素(IL)10急性治疗可抑制用HIV-1(59)接种的thy / liv-SCID-hu小鼠血浆病毒血症和HIV感染的发展,但不能抑制人IL-12。这些修饰的thy / liv-SCID-hu小鼠中的人外周血单核细胞对用外源细胞因子进行的体内治疗有反应。 IL-12处理可诱导人外周血单个核细胞中人干扰素γ的表达,IL-10处理可抑制人γ的表达。因此,这些修饰的thy / liv-SCID-hu小鼠应被证明是有价值的体内模型,用于检查免疫调节疗法在改善HIV感染中的作用。此外,我们对IL-10对急性HIV感染的体内抑制作用的证明表明,可能有必要进行进一步的研究,以评估IL-10治疗是否在预防HIV感染后的个体中预防HIV感染方面是否起作用,例如感染艾滋病毒的母亲所生的孩子。

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