Fas ligand deficiency in HIV disease

Apoptosis is postulated to be involved as an anti-viral immune mechanism by killing infected cells before viral replication has occurred. The Fas–Fas ligand interaction is a powerful regulator of T cell apoptosis and could potentially act as a potent anti-viral immune mechanism against T cell tropic virus such as human immunodeficiency virus (HIV). We investigated the status of Fas ligand in peripheral blood mononuclear cells (PBMCs) obtained from persons infected with HIV. We found that monocytes in freshly isolated PBMCs from healthy individuals possess cell surface Fas ligand. In contrast, monocytes in freshly isolated PBMCs from HIV-infected patients had no detectable Fas ligand on the cell surface. Consistent with these findings of surface expression, Fas ligand activity was deficient in the cells from HIV-infected persons. The effect of replacing Fas ligand activity on HIV production by patients’ cells was assessed in an in vitro assay. The addition of a functional anti-Fas antibody to PBMCs from HIV-infected individuals inhibited viral production by greater than 90% without affecting lymphocytic function. These findings suggest the possibility of a new therapeutic modality for the treatment of HIV-infected individuals based on the reconstitution of Fas ligand activity.

细胞凋亡（Apoptosis）被认为可作为一种抗病毒免疫机制，在病毒完成复制前杀灭受感染细胞。Fas-Fas配体（Fas–Fas ligand）相互作用是调控T细胞凋亡的关键通路，有望作为强效抗病毒免疫机制，对抗诸如人类免疫缺陷病毒（HIV）这类嗜T细胞病毒。本研究针对HIV感染者来源的外周血单个核细胞（peripheral blood mononuclear cells，PBMCs）中Fas配体的表达状态展开探究。研究发现，健康个体新鲜分离的PBMCs中的单核细胞，其细胞表面可检测到Fas配体表达；与之相反，HIV感染者新鲜分离的PBMCs中的单核细胞，细胞表面无法检测到Fas配体。与上述表面表达的检测结果相符，HIV感染者的细胞中Fas配体活性存在缺陷。本研究通过体外实验（in vitro assay）评估了修复Fas配体活性对感染者细胞产生HIV的影响。向HIV感染者的PBMCs中添加功能性抗Fas抗体，可抑制超过90%的病毒产生，且不会对淋巴细胞功能造成影响。上述研究结果提示，基于重建Fas配体活性的新型治疗策略，有望为HIV感染者的临床治疗提供新方向。