Wherry E John, Day Cheryl L, Draenert Rika, Miller Joseph D, Kiepiela Photini, Woodberry Tonia, Brander Christian, Addo Marylyn, Klenerman Paul, Ahmed Rafi, Walker Bruce D
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Virology. 2006 Sep 30;353(2):366-73. doi: 10.1016/j.virol.2006.06.017. Epub 2006 Jul 24.
Chronic infections in mice can result in defects in memory CD8 T cell properties including low expression of the IL-7Ralpha (CD127). To determine whether defects in memory CD8 T cell formation exist during human chronic infections and to what extent these defects may be allele- or epitope-specific, we compared influenza (Flu), vaccinia (VV) and EBV-specific CD8 T cells to HIV-specific CD8 T cells, using a panel of 13 HIV tetramers. Compared to Flu, VV or EBV, HIV tetramer+ CD8 T cells expressed significantly lower levels of CD127, and this reduction was pervasive across all epitopes and alleles tested and over a wide range of viral loads and CD4 counts. These results indicate impaired HIV-specific memory CD8 T cell differentiation, regardless of level of control of viremia, epitopes targeted or restricting HLA alleles.
小鼠中的慢性感染可导致记忆性CD8 T细胞特性出现缺陷,包括IL-7Rα(CD127)表达降低。为了确定人类慢性感染期间记忆性CD8 T细胞形成是否存在缺陷,以及这些缺陷在何种程度上可能是等位基因或表位特异性的,我们使用一组13种HIV四聚体,将流感(Flu)、痘苗病毒(VV)和EBV特异性CD8 T细胞与HIV特异性CD8 T细胞进行了比较。与Flu、VV或EBV相比,HIV四聚体+ CD8 T细胞表达的CD127水平显著更低,且这种降低在所有测试的表位和等位基因中普遍存在,并且在广泛的病毒载量和CD4计数范围内均如此。这些结果表明,无论病毒血症的控制水平、靶向的表位或限制性HLA等位基因如何,HIV特异性记忆性CD8 T细胞的分化均受损。