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Evaluation of Cytotoxic T-Lymphocyte Responses in Human and Nonhuman Primate Subjects Infected with Human Immunodeficiency Virus Type 1 or Simian/Human Immunodeficiency Virus

机译:评价感染人类免疫缺陷病毒1型或猿猴/人类免疫缺陷病毒的人类和非人类灵长类动物的细胞毒性T淋巴细胞反应

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摘要

Cytotoxic T-lymphocyte (CTL) responses have been implicated as playing an important role in control of human immunodeficiency virus (HIV) infection. However, it is technically difficult to demonstrate CTL responses consistently in nonhuman primate and human subjects using traditional cytotoxicity assay methods. In this study, we systematically evaluated culture conditions that may affect the proliferation and expansion of CTL effector cells and presented a sensitive method for detection of cytotoxicity responses with bulk CTL cultures. We confirmed the sensitivity and specificity of this method by demonstration of vigorous CTL responses in a simian-HIV (SHIV)-infected rhesus macaque. The expansion of epitope-specific CTL effector cells was also measured quantitatively by CTL epitope-major histocompatibility complex tetramer complex staining. In addition, two new T-cell determinants in the SIV gag region are identified. Last, we showed the utility of this method for studying CTL responses in chimpanzee and human subjects.
机译:细胞毒性T淋巴细胞(CTL)反应已被认为在控制人类免疫缺陷病毒(HIV)感染中起着重要作用。然而,使用传统的细胞毒性测定方法在非人类灵长类动物和人类受试者中一致地证明CTL反应在技术上是困难的。在这项研究中,我们系统地评估了可能影响CTL效应细胞增殖和扩展的培养条件,并提出了一种检测大量CTL培养物细胞毒性反应的灵敏方法。我们通过在猿猴-HIV(SHIV)感染的猕猴中表现出强烈的CTL反应,证实了该方法的敏感性和特异性。还通过CTL表位-主要组织相容性复合物四聚体复合物染色定量测量了表位特异性CTL效应细胞的扩增。此外,在SIV gag区域发现了两个新的T细胞决定簇。最后,我们展示了该方法在研究黑猩猩和人类受试者的CTL反应中的实用性。

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