Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Blood. 2010 Apr 15;115(15):3070-8. doi: 10.1182/blood-2009-10-245225. Epub 2010 Feb 10.
One of the most puzzling observations in HIV research is the lack of pathogenicity in most nonhuman primate species that are natural hosts of simian immunodeficiency virus (SIV) infection. Despite this, natural hosts experience a level of viremia similar to humans infected with HIV or macaques infected with SIV. To determine the role of adaptive immune responses in viral containment and lack of disease, we delayed the generation of cellular and humoral immune responses by administering anti-CD8- and anti-CD20 lymphocyte-depleting antibodies to sabaeus African green monkeys (Chlorocebus sabaeus) before challenge with SIV(sab9315BR). In vivo lymphocyte depletion during primary infection resulted in a brief elevation of viremia but not in disease. Based on the magnitude and timing of SIV-specific CD8(+) T-cell responses in the lymphocyte-depleted animals, CD8(+) T-cell responses appear to contribute to viral containment in natural hosts. We found no evidence for a contribution of humoral immune responses in viral containment. These studies indicate that natural hosts have developed mechanisms in addition to classic adaptive immune responses to cope with this lentiviral infection. Thus, adaptive immune responses in natural hosts appear to be less critical for viral containment than in HIV infection.
在 HIV 研究中,最令人费解的观察之一是,在大多数自然感染猴免疫缺陷病毒(SIV)的非人类灵长类动物物种中,缺乏致病性。尽管如此,自然宿主的病毒血症水平与感染 HIV 的人类或感染 SIV 的猕猴相似。为了确定适应性免疫反应在病毒控制和疾病缺乏中的作用,我们在 SIV(sab9315BR) 感染前,通过给予抗 CD8 和抗 CD20 淋巴细胞耗竭抗体来延迟沙氏食蟹猴(Chlorocebus sabaeus)的细胞和体液免疫反应的产生。在原发性感染期间进行体内淋巴细胞耗竭导致病毒血症短暂升高,但不会导致疾病。基于淋巴细胞耗竭动物中 SIV 特异性 CD8(+) T 细胞反应的幅度和时间,CD8(+) T 细胞反应似乎有助于自然宿主中的病毒控制。我们没有发现体液免疫反应在病毒控制中的作用的证据。这些研究表明,自然宿主除了经典的适应性免疫反应外,还发展了应对这种慢病毒感染的机制。因此,自然宿主中的适应性免疫反应对于病毒控制似乎不如 HIV 感染中那么关键。