title: Increased frequency of Tim-3 expressing T cells is associated with symptomatic West Nile virus infection.
abstract: More than a decade after West Nile virus (WNV) entered North America, and despite a significant increase in reported cases during the 2012 and 2013 seasons, no treatment or vaccine for humans is available. Although antiviral T cells contribute to the control of WNV, little is known about their regulation during acute infection. We analyzed the expression of Tim-3 and PD-1, two recently identified T cell negative immune checkpoint receptors, over the course of WNV infection. Symptomatic WNV+ donors exhibited higher frequencies of Tim-3+ cells than asymptomatic subjects within naïve/early differentiated CD28+/-CD57-CD4+ and differentiated CD28-CD57-CD8+ T cells. Our study links Tim-3-expression on T cells during acute WNV infection with the development of symptomatic disease, suggesting Tim-3 and its ligands could be targeted therapeutically to alter anti-WNV immunity and improve disease outcome.
authors.affiliation: Blood Systems Research Institute, University of California at San Francisco, San Francisco, California, United States of America.
authors.forename: Marion C
authors.initials: MC
authors.lastname: Lanteri
authors.affiliation: Departments of Medicine, Molecular Microbiology, and Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.affiliation: Blood Systems Research Institute, University of California at San Francisco, San Francisco, California, United States of America.
authors.forename: Jacqueline P
authors.initials: JP
authors.lastname: Law
authors.affiliation: Department of Tropical Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Glen M
authors.initials: GM
authors.lastname: Chew
authors.affiliation: Blood Systems Research Institute, University of California at San Francisco, San Francisco, California, United States of America.
authors.forename: Shiquan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Blood Systems Research Institute, University of California at San Francisco, San Francisco, California, United States of America.
authors.forename: Heather C
authors.initials: HC
authors.lastname: Inglis
authors.affiliation: Blood Systems Research Institute, University of California at San Francisco, San Francisco, California, United States of America.
authors.forename: Derek
authors.initials: D
authors.lastname: Wong
authors.affiliation: Blood Systems Research Institute, University of California at San Francisco, San Francisco, California, United States of America; Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.affiliation: Blood Systems Research Institute, University of California at San Francisco, San Francisco, California, United States of America; Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America; Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
authors.affiliation: Department of Tropical Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, United States of America.
authors.forename: Lishomwa C
authors.initials: LC
authors.lastname: Ndhlovu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058070:Asymptomatic Diseases; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018959:CD57 Antigens / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D005260:Female; D015870:Gene Expression; D000072597:Hepatitis A Virus Cellular Receptor 2; D054884:Host-Pathogen Interactions; D006801:Humans; D016130:Immunophenotyping; D018655:Lymphocyte Count; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology; D012720:Severity of Illness Index; D014901:West Nile Fever / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000821:virology; D014902:West Nile virus / Q000502:physiology*
chemical_list: D018106:CD28 Antigens; D018959:CD57 Antigens; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor