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Int. J. Mol. Sci. 2018, 19(7), 2000; https://doi.org/10.3390/ijms19072000

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

1
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden
2
Department of Medicine Huddinge, Unit of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Received: 1 June 2018 / Revised: 29 June 2018 / Accepted: 6 July 2018 / Published: 9 July 2018
(This article belongs to the Collection Advances in Proteomic Research)
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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. View Full-Text
Keywords: biomarker; human immunodeficiency virus (HIV); immune checkpoint; programmed cell death protein 1 (PD-1); T cell exhaustion biomarker; human immunodeficiency virus (HIV); immune checkpoint; programmed cell death protein 1 (PD-1); T cell exhaustion
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Sperk, M.; Domselaar, R.; Neogi, U. Immune Checkpoints as the Immune System Regulators and Potential Biomarkers in HIV-1 Infection. Int. J. Mol. Sci. 2018, 19, 2000.

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