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

Int J Mol Sci. 2018 Jul 9;19(7):2000. doi: 10.3390/ijms19072000.

Abstract

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.

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

Publication types

  • Review

MeSH terms

  • Antibodies / pharmacology
  • Antibodies / therapeutic use*
  • Antigens, CD / metabolism
  • B7-H1 Antigen / metabolism
  • Biomarkers / metabolism*
  • CTLA-4 Antigen / metabolism
  • Disease Progression
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / immunology*
  • Hepatitis A Virus Cellular Receptor 2 / metabolism
  • Humans
  • Lymphocyte Activation Gene 3 Protein
  • Programmed Cell Death 1 Receptor / metabolism

Substances

  • Antibodies
  • Antigens, CD
  • B7-H1 Antigen
  • Biomarkers
  • CD274 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Lymphocyte Activation Gene 3 Protein