Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, District of Columbia, USA.
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
J Infect Dis. 2020 Oct 1;222(9):1540-1549. doi: 10.1093/infdis/jiaa269.
In chronic HIV infection, virus-specific cytotoxic CD8 T cells showed expression of checkpoint receptors and impaired function. Therefore, restoration of CD8 T-cell function is critical in cure strategies. Here, we show that in vitro blockade of programmed cell death ligand 1 (PD-L1) by an anti-PD-L1 antibody (avelumab) in combination with recombinant human interleukin-15 (rhIL-15) synergistically enhanced cytokine secretion by proliferating HIVGag-specific CD8 T cells. In addition, these CD8 T cells have a CXCR3+PD1-/low phenotype, suggesting a potential to traffic into peripheral tissues. In vitro, proliferating CD8 T cells express PD-L1 suggesting that anti-PD-L1 treatment also targets virus-specific CD8 T cells. Together, these data indicate that rhIL-15/avelumab combination therapy could be a useful strategy to enhance CD8 T-cell function in cure strategies.
在慢性 HIV 感染中，病毒特异性细胞毒性 CD8 T 细胞表现出检查点受体的表达和功能受损。因此，恢复 CD8 T 细胞功能是治愈策略的关键。在这里，我们表明，体外阻断程序性细胞死亡配体 1（PD-L1）的抗 PD-L1 抗体（avelumab）与重组人白细胞介素-15（rhIL-15）联合使用可协同增强增殖的 HIVGag 特异性 CD8 T 细胞细胞因子的分泌。此外，这些 CD8 T 细胞具有 CXCR3+PD1-/low 表型，提示有可能进入外周组织。在体外，增殖的 CD8 T 细胞表达 PD-L1，表明抗 PD-L1 治疗也靶向病毒特异性 CD8 T 细胞。总之，这些数据表明 rhIL-15/avelumab 联合治疗可能是增强治愈策略中 CD8 T 细胞功能的一种有用策略。
