McKay Paul F, Schmitz Jörn E, Barouch Dan H, Kuroda Marcelo J, Lifton Michelle A, Nickerson Christine E, Gorgone Darci A, Letvin Norman L
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
J Immunol. 2002 Jan 1;168(1):332-7. doi: 10.4049/jimmunol.168.1.332.
Accumulating evidence suggests that HIV-specific CD8(+) CTL are dysfunctional in HIV-infected individuals with progressive clinical disease. In the present studies, cytokine production by virus-specific CTL was assessed in the rhesus monkey model for AIDS to determine its contribution to the functional impairment of CTL. CTL from monkeys infected with nonpathogenic isolates of simian and simian-human immunodeficiency virus expressed high levels of IFN-gamma, TNF-alpha, and IL-2 after in vitro exposure to a nonspecific mitogen or the optimal peptide representing a dominant virus-specific CTL epitope. However, similarly performed studies assessing these capabilities in CTL from monkeys infected with pathogenic immunodeficiency virus isolates demonstrated a significant dysfunction in the ability of the CTL to produce IL-2 and TNF-alpha. Importantly, CTL from vaccinated monkeys that effectively controlled the replication of a highly pathogenic simian-human immunodeficiency virus isolate following challenge demonstrated a preserved capacity to produce these cytokines. These experiments suggest that defects in cytokine production may contribute to CTL dysfunction in chronic HIV or SIV infection. Moreover, an AIDS vaccine that confers protection against clinical disease evolution in this experimental model also preserves the functional capacity of these CTL to produce both IL-2 and TNF-alpha.
越来越多的证据表明，在患有进行性临床疾病的艾滋病病毒感染者中，艾滋病病毒特异性CD8(+) 细胞毒性T淋巴细胞（CTL）功能失调。在本研究中，我们在恒河猴艾滋病模型中评估了病毒特异性CTL产生细胞因子的情况，以确定其对CTL功能损伤的影响。感染猿猴和猿猴 - 人类免疫缺陷病毒非致病性分离株的猴子的CTL，在体外暴露于非特异性有丝分裂原或代表主要病毒特异性CTL表位的最佳肽后，表达高水平的γ干扰素、肿瘤坏死因子 - α和白细胞介素 - 2。然而，在感染致病性免疫缺陷病毒分离株的猴子的CTL中进行的类似研究评估这些能力时发现，CTL产生白细胞介素 - 2和肿瘤坏死因子 - α的能力存在明显功能障碍。重要的是，在接种疫苗的猴子受到高致病性猿猴 - 人类免疫缺陷病毒分离株攻击后能有效控制其复制的CTL，显示出产生这些细胞因子的能力得以保留。这些实验表明，细胞因子产生缺陷可能导致慢性艾滋病病毒或猴免疫缺陷病毒感染中的CTL功能障碍。此外，在该实验模型中能预防临床疾病进展的艾滋病疫苗也能保留这些CTL产生白细胞介素 - 2和肿瘤坏死因子 - α的功能能力。
