Steger K K, Waterman P M, Pauza C D
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, and Wisconsin Regional Primate Research Center, Madison, Wisconsin 53706, USA.
J Virol. 1999 Mar;73(3):1853-9. doi: 10.1128/JVI.73.3.1853-1859.1999.
Simian-human immunodeficiency virus (SHIV) infection in macaques provides a convenient model for testing vaccine efficacy and for understanding viral pathogenesis in AIDS. We immunized macaques with recombinant, Salmonella typhimurium (expressing Gag) or soluble Gag in adjuvant to generate T-cell-dependent lymphoproliferative or serum antibody responses. Immunized animals were challenged by intrarectal inoculation with SHIV89.6PD. Virus infection was accompanied by rapid losses of lymphoproliferative responses to Gag or phytohemagglutinin. By 8 weeks, mitogen responses recovered to near normal levels but antigen-specific immunity remained at low or undetectable levels. Serum antibody levels were elevated initially by virus exposure but soon dropped well below levels achieved by immunization. Our studies show a rapid depletion of preexisting Gag-specific CD4(+) T cells that prevent or limit subsequent antiviral cellular and humoral immune responses during acute SHIV infection.
猕猴感染猿猴-人类免疫缺陷病毒（SHIV）为测试疫苗效力以及了解艾滋病病毒发病机制提供了一个便捷的模型。我们用重组鼠伤寒沙门氏菌（表达Gag）或佐剂中的可溶性Gag免疫猕猴，以产生T细胞依赖性淋巴细胞增殖或血清抗体反应。对免疫动物进行经直肠接种SHIV89.6PD攻击。病毒感染伴随着对Gag或植物血凝素的淋巴细胞增殖反应迅速丧失。到8周时，有丝分裂原反应恢复到接近正常水平，但抗原特异性免疫仍处于低水平或无法检测到的水平。血清抗体水平最初因接触病毒而升高，但很快降至远低于免疫所达到的水平。我们的研究表明，在急性SHIV感染期间，预先存在的Gag特异性CD4(+) T细胞迅速耗竭，从而阻止或限制了随后的抗病毒细胞免疫和体液免疫反应。
