title: Elevated Expression of CD160 and 2B4 Defines a Cytolytic HIV-Specific CD8+ T-Cell Population in Elite Controllers.
abstract: During chronic human immunodeficiency virus (HIV) infection, virus-specific CD8(+) T cells become functionally exhausted. Unlike most chronically infected individuals, elite controllers of HIV retain CD8(+) T-cell polyfunctionality and cytolytic capacity. It remains unclear whether elite controllers manifest T-cell exhaustion similar to subjects with chronic progression of HIV infection. Here we assessed coexpression of PD-1, Lag-3, CD160, and 2B4 as a measure of T-cell exhaustion in a cohort of elite controllers and in chronic progressors. We found that elite controllers have a high proportion of potentially exhausted (PD1(+)CD160(+)2B4(+)) HIV-specific CD8(+) T cells that is comparable to the proportion in chronic progressors. However, elite controllers also harbor a population of HIV-specific CD160(+)2B4(+) CD8(+) T cells that correlates with cytolytic capacity, as measured by perforin expression, a population not commonly present in chronic progressors. We therefore propose that coexpression of CD160 and 2B4 delineates a population of cytolytic CD8(+) T cells important for the control of HIV.
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Carolina
authors.initials: C
authors.lastname: Pombo
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Gostick
authors.affiliation: Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Institute of Infection and Immunity, Cardiff University School of Medicine, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Betts
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002908:Chronic Disease; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005819:Genetic Markers; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D054353:Perforin / Q000235:genetics / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D000071176:Signaling Lymphocytic Activation Molecule Family; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; C114505:CD160 protein, human; C084093:CD244 protein, human; D058851:GPI-Linked Proteins; D005819:Genetic Markers; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012367:RNA, Viral; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D054353:Perforin; D000093322:Lymphocyte Activation Gene 3 Protein
keywords: 2B4; CD160; CD8+ T cells; HIV; PD-1; T-cell exhaustion; elite controllers