title: Revisiting immune exhaustion during HIV infection.
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.
authors.affiliation: Department of Pediatrics, New York University School of Medicine, NY 10016, USA. Alka.Khaitan@nyumc.org
authors.forename: Alka
authors.initials: A
authors.lastname: Khaitan
authors.forename: Derya
authors.initials: D
authors.lastname: Unutmaz
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D060908:CTLA-4 Antigen; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000093322:Lymphocyte Activation Gene 3 Protein