title: Intracellular cytokine production by dengue virus-specific T cells correlates with subclinical secondary infection.
abstract: The pathophysiology of dengue virus infection remains poorly understood, although secondary infection is strongly associated with more severe disease. In the present study, we performed a nested, case-control study comparing the responses of pre-illness peripheral blood mononuclear cells between children who would subsequently develop either subclinical or symptomatic secondary infection 6-11 months after the baseline blood samples were obtained and frozen. We analyzed intracellular cytokine production by CD4(+) and CD8(+) cells in response to stimulation with dengue antigen. We found higher frequencies of dengue virus-specific TNFα, IFNγ-, and IL-2-producing T cells among schoolchildren who subsequently developed subclinical infection, compared with those who developed symptomatic secondary dengue virus infection. Although other studies have correlated immune responses during secondary infection with severity of disease, to our knowledge this is the first study to demonstrate a pre-infection dengue-specific immune response that correlates specifically with a subclinical secondary infection.
authors.affiliation: Center For Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Hatch
authors.forename: Tim P
authors.initials: TP
authors.lastname: Endy
authors.forename: Stephen
authors.initials: S
authors.lastname: Thomas
authors.forename: Anuja
authors.initials: A
authors.lastname: Mathew
authors.forename: James
authors.initials: J
authors.lastname: Potts
authors.forename: Pamela
authors.initials: P
authors.lastname: Pazoles
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Libraty
authors.forename: Robert
authors.initials: R
authors.lastname: Gibbons
authors.forename: Alan L
authors.initials: AL
authors.lastname: Rothman
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D016207:Cytokines / Q000096:biosynthesis*; D003715:Dengue / Q000276:immunology* / Q000473:pathology*; D003716:Dengue Virus / Q000276:immunology*; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines