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

• Published in: International journal of molecular sciences Vol. 19; no. 7; p. 2000
• Main Authors: Sperk, Maike, Domselaar, Robert van, Neogi, Ujjwal
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.07.2018; MDPI
• Subjects: Apoptosis; biomarker; Biomarkers; Cancer; CD40L protein; CD70 antigen; Cell activation; Cell death; Chronic infection; CTLA-4 protein; Cytotoxicity; Exhaustion; HIV; Human immunodeficiency virus; human immunodeficiency virus (HIV); Immune checkpoint; Immune response (cell-mediated); Infections; Infectious diseases; Lymphocytes; Lymphocytes T; Medicin och hälsovetenskap; Mucin; PD-1 protein; PD-L1 protein; programmed cell death protein 1 (PD-1); Proteins; Regulators; Review; T cell exhaustion; Therapeutic applications; T cell exhaustion; human immunodeficiency virus (HIV); biomarker; programmed cell death protein 1 (PD-1); immune checkpoint
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19072000

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.