Increased frequency of Tim-3 expressing T cells is associated with symptomatic West Nile virus infection

Marion C Lanteri; Michael S Diamond; Jacqueline P Law; Glen M Chew; Shiquan Wu; Heather C Inglis; Derek Wong; Michael P Busch; Philip J Norris; Lishomwa C Ndhlovu

doi:10.1371/journal.pone.0092134

Increased frequency of Tim-3 expressing T cells is associated with symptomatic West Nile virus infection

PLoS One. 2014 Mar 18;9(3):e92134. doi: 10.1371/journal.pone.0092134. eCollection 2014.

Authors

Affiliations

¹ Blood Systems Research Institute, University of California at San Francisco, San Francisco, California, United States of America.
² Departments of Medicine, Molecular Microbiology, and Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
³ Department of Tropical Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, United States of America.
⁴ 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.
⁵ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adolescent
Adult
Aged
Asymptomatic Diseases
CD28 Antigens / genetics
CD28 Antigens / immunology
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / metabolism*
CD4-Positive T-Lymphocytes / pathology
CD4-Positive T-Lymphocytes / virology
CD57 Antigens / genetics
CD57 Antigens / immunology
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / metabolism*
CD8-Positive T-Lymphocytes / pathology
CD8-Positive T-Lymphocytes / virology
Female
Gene Expression
Hepatitis A Virus Cellular Receptor 2
Host-Pathogen Interactions
Humans
Immunophenotyping
Lymphocyte Count
Male
Membrane Proteins / genetics*
Membrane Proteins / immunology
Middle Aged
Programmed Cell Death 1 Receptor / genetics
Programmed Cell Death 1 Receptor / immunology
Severity of Illness Index
West Nile Fever / genetics*
West Nile Fever / immunology
West Nile Fever / pathology
West Nile Fever / virology
West Nile virus / physiology*

Substances

CD28 Antigens
CD57 Antigens
HAVCR2 protein, human
Hepatitis A Virus Cellular Receptor 2
Membrane Proteins
PDCD1 protein, human
Programmed Cell Death 1 Receptor

Abstract

Publication types

MeSH terms

Substances

Grants and funding