Nature Medicine
9, 921 - 927 (2003)
Published online: 15 June 2003; | doi:10.1038/nm887
Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic feverJuthathip Mongkolsapaya1, 2, 7, Wanwisa Dejnirattisai2, 7, Xiao-ning Xu1, Sirijitt Vasanawathana3, Nattaya Tangthawornchaikul4, Aroonrung Chairunsri2, Siraporn Sawasdivorn6, Thaneeya Duangchinda1, Tao Dong1, Sarah Rowland-Jones1, 5, Pa-thai Yenchitsomanus2, Andrew McMichael1, Prida Malasit2, 4
& Gavin Screaton1, 51
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, UK. 2
Medical Molecular Biology Unit, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok noi, Bangkok 10700, Thailand. 3
Pediatric Department, Khon Kaen Hospital, Ministry of Public Health, Khonkaen 40000, Thailand. 4
Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA) Patumthani 12120, Thailand. 5
Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK. 6
Queen Sirikit National Institute of Child Health, Bangkok 10400, Thailand. 7
These authors contributed equally to this work.
Correspondence should be addressed to Prida Malasit sipml@mahidol.ac.th or Gavin Screaton screaton@molbiol.ox.ac.ukDengue 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.
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