title: Cross-reactivity and expansion of dengue-specific T cells during acute primary and secondary infections in humans.
abstract: Serotype-cross-reactive memory T cells responding to secondary dengue virus (DENV) infection are thought to contribute to disease. However, epitope-specific T cell responses have not been thoroughly compared between subjects with primary versus secondary DENV infection. We studied CD8(+) T cells specific for the HLA-A*1101-restricted NS3(133) epitope in a cohort of A11(+) DENV-infected patients throughout acute illness and convalescence. We compared the expansion, serotype-cross-reactivity, and activation of these cells in PBMC from patients experiencing primary or secondary infection and mild or severe disease by flow cytometry. Our results show expansion and activation of DENV-specific CD8(+) T cells during acute infection, which are predominantly serotype-cross-reactive regardless of DENV infection history. These data confirm marked T cell activation and serotype-cross-reactivity during the febrile phase of dengue; however, A11-NS3(133)-specific responses did not correlate with prior antigenic exposure or current disease severity.
authors.affiliation: Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Friberg
authors.forename: Hema
authors.initials: H
authors.lastname: Bashyam
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyosaki-Maeda
authors.forename: James A
authors.initials: JA
authors.lastname: Potts
authors.forename: Thomas
authors.initials: T
authors.lastname: Greenough
authors.forename: Siripen
authors.initials: S
authors.lastname: Kalayanarooj
authors.forename: Robert V
authors.initials: RV
authors.lastname: Gibbons
authors.forename: Ananda
authors.initials: A
authors.lastname: Nisalak
authors.forename: Anon
authors.initials: A
authors.lastname: Srikiatkhachorn
authors.forename: Sharone
authors.initials: S
authors.lastname: Green
authors.forename: Henry A F
authors.initials: HA
authors.lastname: Stephens
authors.forename: Alan L
authors.initials: AL
authors.lastname: Rothman
authors.forename: Anuja
authors.initials: A
authors.lastname: Mathew
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D060085:Coinfection / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D003715:Dengue / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn