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PMID: 21188556 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Revisiting immune exhaustion during HIV infection.

Current HIV/AIDS reports ·Vol. 8 ·No. 1 ·2011-03-00 ·Pages 4-11

Khaitan A, Unutmaz D

Abstract

Chronic immune activation is a hallmark of HIV infection, yet the underlying triggers of immune activation remain unclear. Persistent antigenic stimulation during HIV infection may also lead to immune exhaustion, a phenomenon in which effector T cells become dysfunctional and lose effector functions and proliferative capacity. Several markers of immune exhaustion, such as PD-1, LAG-3, Tim-3, and CTLA-4, which are also negative regulators of immune activation, are preferentially upregulated on T cells during HIV infection. It is not yet clear whether accumulation of T cells expressing activation inhibitory molecules is a consequence of general immune or chronic HIV-specific immune activation. Importantly, however, in vitro blockade of PD-1 and Tim-3 restores HIV-specific T-cell responses, indicating potential for immunotherapies. In this review we discuss the evolution of our understanding of immune exhaustion during HIV infection, highlighting novel markers and potential therapeutic targets.

MeSH Terms
Animals Antigens, CD/immunology Apoptosis Regulatory Proteins/immunology CD4-Positive T-Lymphocytes/virology CD8-Positive T-Lymphocytes/virology CTLA-4 Antigen HIV/immunology HIV Infections/immunology Hepatitis A Virus Cellular Receptor 2 Humans Lymphocyte Activation Membrane Proteins/immunology Programmed Cell Death 1 Receptor Simian Immunodeficiency Virus/immunology T-Lymphocytes/immunology,metabolism
Chemicals
Antigens, CD Apoptosis Regulatory Proteins CD223 antigen CTLA-4 Antigen CTLA4 protein, human HAVCR2 protein, human Hepatitis A Virus Cellular Receptor 2 Membrane Proteins PDCD1 protein, human Programmed Cell Death 1 Receptor
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Khaitan Alka
Department of Pediatrics, New York University School of Medicine, NY 10016, USA. [email protected]
Unutmaz Derya
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Article Info
Journal
Current HIV/AIDS reports
Abbr.
Curr HIV/AIDS Rep
ISSN
1548-3576
DOI
10.1007/s11904-010-0066-0
Email
[email protected]
Published
2011-03-00
Pages
4-11
Language
English
Region
United States
NLM ID
101235661
PMCID
PMC3144861
Subset
IM
Grants
NIAID NIH HHS · R21 AI087973 · United States
NIAID NIH HHS · R21 AI087973-01A1 · United States
NCRR NIH HHS · 1 UL1 RR029893 · United States
NIAID NIH HHS · R21AI087973-01 · United States
External Links
PubMed source DOI: 10.1007/s11904-010-0066-0 PMC Full Text View journal details
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