Antiviral Inhibitory Capacity of CD8+ T cells Predicts the Rate of CD4+ T-Cell Decline in HIV-1 Infection

作者：Yang, Hongbing; Wu, Hao; Hancock, Gemma; Clutton, Genevieve; Sande, Nellia; Xu, Xiaoning; Yan, Huiping; Huang, Xiaojie; Angus, Brian; Kuldanek, Kristin; Fidler, Sarah; Denny, Thomas N.; Birks, Jacqueline; McMichael, Andrew; Dorrell, Lucy^*

来源：Journal of Infectious Diseases, 2012, 206(4): 552-561.

DOI：10.1093/infdis/jis379

• HUMAN-IMMUNODEFICIENCY-VIRUS
• FUNCTIONAL PROFILE
• IMMUNE CONTROL
• VIRAL LOAD
• RNA LEVELS
• EX-VIVO
• VACCINE
• RESPONSES
• VIREMIA
• IMMUNIZATION

Background. Rare human immunodeficiency virus type 1 (HIV-1)-infected individuals who maintain control of viremia without therapy show potent CD8+ T-cell-mediated suppression of viral replication in vitro. Whether this is a determinant of the rate of disease progression in viremic individuals is unknown. @@@ Methods. We measured CD8+ T-cell-mediated inhibition of a heterologous HIV-1 isolate in 50 HIV-1-seropositive adults with diverse progression rates. Linear mixed models were used to determine whether CD8+ T-cell function could explain variation in the rate of CD4+ T-cell decline. @@@ Results. There was a significant interaction between CD8+ T-cell antiviral activity in vitro and the rate of CD4+ T-cell decline in chronically infected individuals (P < .0001). In a second prospective analysis of recently infected subjects followed for up to 3 years, CD8+ T-cell antiviral activity strongly predicted subsequent CD4+ T-cell decline (P < .0001) and explained up to 73% of the interindividual variation in the CD4+ T-cell slope. In addition, it was inversely associated with viral load set point (r = -0.68 and P = .002). @@@ Conclusions. The antiviral inhibitory capacity of CD8+ T cells is highly predictive of CD4+ T-cell loss in early HIV-1 infection. It has potential as a benchmark of effective immunity in vaccine evaluation.

• 出版日期2012-8-15
• 单位首都医科大学