Jensen Sanne Skov, Fomsgaard Anders, Larsen Tine Kochendorf, Tingstedt Jeanette Linnea, Gerstoft Jan, Kronborg Gitte, Pedersen Court, Karlsson Ingrid
Virus Research & Development Laboratory, Department of Microbial Diagnostic and Virology, Statens Serum Institut, Copenhagen, Denmark; Department of Infectious Diseases, Odense University Hospital, Odense, Denmark; Infectious Disease Research Unit, Clinical Institute, University of Southern Denmark, Odense, Denmark.
Virus Research & Development Laboratory, Department of Microbial Diagnostic and Virology, Statens Serum Institut, Copenhagen, Denmark; Infectious Disease Research Unit, Clinical Institute, University of Southern Denmark, Odense, Denmark.
PLoS One. 2015 Oct 1;10(10):e0139573. doi: 10.1371/journal.pone.0139573. eCollection 2015.
CD8+ T cell-restricted immunity is important in the control of HIV-1 infection, but continued immune activation results in CD8+ T cell dysfunction. Early initiation of antiretroviral treatment (ART) and the duration of ART have been associated with immune reconstitution. Here, we evaluated whether restoration of CD8+ T cell function in HIV-1-infected individuals was dependent on early initiation of ART. HIV-specific CD107a, IFNγ, IL-2, TNFα and MIP-1β expression by CD8+ T cells and the frequency of CD8+ T cells expressing PD-1, 2B4 and CD160 were measured by flow cytometry. The frequency of CD8+ T cells expressing the inhibitory markers PD-1, 2B4 and CD160 was lower in ART-treated individuals compared with ART-naïve individuals and similar to the frequency in HIV-uninfected controls. The expression of the three markers was similarly independent of when therapy was initiated. Individuals treated before seroconversion displayed an HIV-specific CD8+ T cell response that included all five functional markers; this was not observed in individuals treated after seroconversion or in ART-naïve individuals. In summary, ART appears to restore the total CD8+ T cell population to a less exhausted phenotype, independent of the time point of initiation. However, to preserve multifunctional, HIV-1-specific CD8+ T cells, ART might have to be initiated before seroconversion.
CD8+ T细胞限制性免疫在控制HIV-1感染中很重要，但持续的免疫激活会导致CD8+ T细胞功能障碍。抗逆转录病毒治疗（ART）的早期启动和治疗持续时间与免疫重建有关。在这里，我们评估了HIV-1感染者中CD8+ T细胞功能的恢复是否依赖于ART的早期启动。通过流式细胞术测量CD8+ T细胞的HIV特异性CD107a、IFNγ、IL-2、TNFα和MIP-1β表达以及表达PD-1、2B4和CD160的CD8+ T细胞频率。与未接受ART治疗的个体相比，接受ART治疗的个体中表达抑制性标志物PD-1、2B4和CD160的CD8+ T细胞频率较低，且与未感染HIV的对照频率相似。这三种标志物的表达同样与治疗开始时间无关。在血清转换前接受治疗的个体表现出包括所有五种功能标志物的HIV特异性CD8+ T细胞反应；在血清转换后接受治疗的个体或未接受ART治疗的个体中未观察到这种情况。总之，ART似乎能将总的CD8+ T细胞群体恢复到较少耗竭的表型，与启动时间点无关。然而，为了保留多功能的、HIV-1特异性的CD8+ T细胞，ART可能必须在血清转换前启动。
