Sirianni Maria Caterina, Vincenzi Laura, Topino Simone, Giovannetti Antonello, Mazzetta Francesca, Libi Fabio, Scaramuzzi Donato, Andreoni Massimo, Pinter Elena, Baccarini Sara, Rezza Giovanni, Monini Paolo, Ensoli Barbara
Department of Clinical Immunology, University of Rome La Sapienza, Viale dell'Università 37, I-00185 Rome, Italy.
Eur J Immunol. 2002 Oct;32(10):2711-20. doi: 10.1002/1521-4141(2002010)32:10<2711::AID-IMMU2711>3.0.CO;2-3.
Kaposi's sarcoma (KS) develops upon reactivation of human herpesvirus 8 (HHV8) infection and virus dissemination to blood and tissue cells, including endothelial and KS spindle cells where the virus is mostly present in a latent form. However, this may likely require the presence of compromised host immune responses and/or the evasion of infected cells from the host immune response. In this regard, mechanisms of evasion of productively infected cells from both CTL and NK cell responses, and resistance of latently infected cells from specific CTL, have already been shown. Here we show that cells which are latently infected by HHV8 are indeed efficiently lysed by NK cells from individuals with a normal immune response. Notably, NK cell-mediated immunity was found to be significantly reduced in AIDS patients with progressing KS as compared to both HIV-negative patients with indolent classic KS or normal blood donors. However, it was restored after treatment with the highly active antiretroviral therapy (HAART) in AIDS-KS patients, that showed regression and clearance of HHV8 from PBMC. By contrast, AIDS-KS patients with a more aggressive disease and no clinical response had persistent HHV8 viremia associated with reduced NK cell cytotoxicity. These results suggest a key role for NK cells in the control of HHV8 latent infection, KS development, and in disease remission upon HAART.
卡波西肉瘤（KS）在人疱疹病毒8型（HHV8）感染重新激活且病毒扩散至血液和组织细胞（包括内皮细胞和KS梭形细胞，病毒大多以潜伏形式存在于这些细胞中）时发生。然而，这可能需要宿主免疫反应受损和/或被感染细胞逃避宿主免疫反应。在这方面，已证实了被有效感染的细胞逃避CTL和NK细胞反应的机制，以及潜伏感染细胞对特异性CTL的抗性。在此我们表明，被HHV8潜伏感染的细胞确实会被免疫反应正常个体的NK细胞有效裂解。值得注意的是，与患有惰性经典KS的HIV阴性患者或正常献血者相比，进展期KS的艾滋病患者中NK细胞介导的免疫显著降低。然而，在接受高效抗逆转录病毒疗法（HAART）治疗后，艾滋病KS患者的NK细胞介导的免疫得以恢复，这些患者的HHV8从外周血单核细胞中消退和清除。相比之下，患有侵袭性更强疾病且无临床反应的艾滋病KS患者存在持续性HHV8病毒血症，且NK细胞细胞毒性降低。这些结果表明NK细胞在控制HHV8潜伏感染、KS发展以及HAART治疗后的疾病缓解中起关键作用。
