title: Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever.
abstract: Dengue virus presents a growing threat to public health in the developing world. Four major serotypes of dengue virus have been characterized, and epidemiological evidence shows that dengue hemorrhagic fever (DHF), the more serious manifestation of the disease, occurs more frequently upon reinfection with a second serotype. We have studied dengue virus-specific T-cell responses in Thai children. During acute infection, few dengue-responsive CD8+ T cells were recovered; most of those present showed an activated phenotype and were undergoing programmed cell death. Many dengue-specific T cells were of low affinity for the infecting virus and showed higher affinity for other, probably previously encountered strains. Profound T-cell activation and death may contribute to the systemic disturbances leading to DHF, and original antigenic sin in the T-cell responses may suppress or delay viral elimination, leading to higher viral loads and increased immunopathology.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
authors.forename: Juthathip
authors.initials: J
authors.lastname: Mongkolsapaya
authors.forename: Wanwisa
authors.initials: W
authors.lastname: Dejnirattisai
authors.forename: Xiao-ning
authors.initials: XN
authors.lastname: Xu
authors.forename: Sirijitt
authors.initials: S
authors.lastname: Vasanawathana
authors.forename: Nattaya
authors.initials: N
authors.lastname: Tangthawornchaikul
authors.forename: Aroonrung
authors.initials: A
authors.lastname: Chairunsri
authors.forename: Siraporn
authors.initials: S
authors.lastname: Sawasdivorn
authors.forename: Thaneeya
authors.initials: T
authors.lastname: Duangchinda
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
authors.forename: Sarah
authors.initials: S
authors.lastname: Rowland-Jones
authors.forename: Pa-thai
authors.initials: PT
authors.lastname: Yenchitsomanus
authors.forename: Andrew
authors.initials: A
authors.lastname: McMichael
authors.forename: Prida
authors.initials: P
authors.lastname: Malasit
authors.forename: Gavin
authors.initials: G
authors.lastname: Screaton
mesh_terms: D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002648:Child; D003716:Dengue Virus / Q000145:classification / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D014644:Genetic Variation; D015234:HLA-A Antigens / Q000276:immunology*; D059870:HLA-A11 Antigen; D006801:Humans; D019595:Severe Dengue / Q000276:immunology* / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D013785:Thailand
chemical_list: D000939:Epitopes; D015234:HLA-A Antigens; D059870:HLA-A11 Antigen