Urbani Simona, Amadei Barbara, Tola Daniela, Massari Marco, Schivazappa Simona, Missale Gabriele, Ferrari Carlo
Laboratorio Immunopatologia Virale, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43100 Parma, Italy.
J Virol. 2006 Nov;80(22):11398-403. doi: 10.1128/JVI.01177-06. Epub 2006 Sep 6.
Hepatitis C virus (HCV)-specific CD8 cell exhaustion may represent a mechanism of HCV persistence. The inhibitory receptor PD-1 has been reported to be up-regulated in exhausted CD8 cells. Therefore, we studied PD-1 expression longitudinally during acute HCV infection. Most HCV-specific CD8 cells expressed PD-1 at the time of acute illness, irrespective of the final outcome. PD-1 expression declined with the acquisition of a memory phenotype and recovery of an efficient CD8 cell function in resolving HCV infections, whereas high levels were maintained when HCV persisted and HCV-specific CD8 cells remained dysfunctional. Blocking PD-1/PDL-1 interaction with an anti-PDL-1 antibody improved the capacity of expansion of virus-specific CD8 cells.
丙型肝炎病毒（HCV）特异性CD8细胞耗竭可能是HCV持续存在的一种机制。据报道，抑制性受体PD-1在耗竭的CD8细胞中上调。因此，我们纵向研究了急性HCV感染期间PD-1的表达。在急性发病时，大多数HCV特异性CD8细胞表达PD-1，无论最终结果如何。在解决HCV感染过程中，随着记忆表型的获得和有效CD8细胞功能的恢复，PD-1表达下降，而当HCV持续存在且HCV特异性CD8细胞仍功能失调时，PD-1水平维持在高位。用抗PDL-1抗体阻断PD-1/PDL-1相互作用可提高病毒特异性CD8细胞的扩增能力。
