Abstract:
During HIV/SIV infection, the upregulation of immune checkpoint (IC) markers, programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), T cell immunoglobulin and ITIM domain (TIGIT), lymphocyte-activation gene-3 (LAG-3), T cell immunoglobulin and mucin domain-3 (Tim-3), CD160, 2B4 (CD244), and V-domain Ig suppressor of T cell activation (VISTA), can lead to chronic T cell exhaustion. These ICs play predominant roles in regulating the progression of HIV/SIV infection by mediating T cell responses as well as enriching latent viral reservoirs. It has been demonstrated that enhanced expression of ICs on CD4+ and CD8+ T cells could inhibit cell proliferation and cytokine production. Overexpression of ICs on CD4+ T cells could also format and prolong HIV/SIV persistence. IC blockers have shown promising clinical results in HIV therapy, implying that targeting ICs may optimize antiretroviral therapy in the context of HIV suppression. Here, we systematically review the expression profile, biological regulation, and therapeutic efficacy of targeted immune checkpoints in HIV/SIV infection.
摘要:
在HIV/SIV感染期间,免疫检查点(IC)标记的上调,程序性细胞死亡蛋白-1(PD-1),细胞毒性T淋巴细胞相关抗原-4(CTLA-4),T细胞免疫球蛋白和ITIM结构域(TIGIT),淋巴细胞激活基因-3(LAG-3),T细胞免疫球蛋白和粘蛋白结构域-3(Tim-3),CD160,2B4(CD244),和T细胞激活的V域Ig抑制因子(VISTA),会导致慢性T细胞衰竭。这些IC通过介导T细胞反应以及富集潜伏的病毒储库在调节HIV/SIV感染的进展中起主要作用。已经证明,ICs在CD4+和CD8+T细胞上的增强表达可以抑制细胞增殖和细胞因子产生。IC在CD4+T细胞上的过表达也可以格式化和延长HIV/SIV的持久性。IC阻滞剂在HIV治疗中显示出了有希望的临床结果,这意味着靶向IC可以在抑制HIV的背景下优化抗逆转录病毒治疗。这里,我们系统地回顾了表达谱,生物调节,以及在HIV/SIV感染中靶向免疫检查点的治疗效果。