Immune Checkpoints as the Immune System Regulators and Potential Biomarkers in HIV-1 Infection

International Journal of Molecular Sciences

Robertvan Domselaar¹  Ujjwal Neogi²  Maike Sperk² 

[1] Department of Medicine Huddinge, Unit of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden;Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden;

关键词: biomarker;    human immunodeficiency virus (HIV);    immune checkpoint;    programmed cell death protein 1 (PD-1);    T cell exhaustion;   

DOI  :  10.3390/ijms19072000

来源: DOAJ

【 摘 要 】

Immune checkpoints are several co-stimulatory and inhibitory pathways that regulate T cell immune responses. Most of the discoveries about immune checkpoints were made in cancer research where inhibitory immune checkpoints cause immune exhaustion and down-regulate anti-tumor responses. In addition to cancer, immune checkpoints are exploited in chronic infectious diseases. In human immunodeficiency virus (HIV) infection, the immune checkpoint molecule called programmed cell death protein 1 (PD-1) has been determined as being a major regulatory factor for T cell exhaustion. Recent studies with antibodies blocking either PD-1 ligand 1 (PD-L1) or PD-1 show not only promising results in the enhancement of HIV-specific immune responses but even in reducing the latent HIV reservoir. Apart from the therapeutic target for a functional cure of HIV-1, immune checkpoint molecules might be used as biomarkers for monitoring disease progression and therapeutic response. In this review, we will summarize and discuss the inhibitory immune checkpoint molecules PD-1, cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte-activation gene 3 (LAG3), and T cell immunoglobulin and mucin-domain-containing-3 (TIM3) as well as the co-stimulatory molecules CD40L and CD70, including their role in immunity, with a particular focus on HIV infection, and being potential targets for a functional HIV cure.

【 授权许可】

Unknown