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.
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Acknowledgements
We thank S. Chunharas at the National Health Foundation, Thailand; M. Mammem and A Nisalak at the Armed Forces Research Institute of Medical Science, Thailand; T. Roston and K. Digleria at the Medical Research Council Human Immunology Unit, UK; P. Petpirin, O. Keawsrikaow, S. Jinatongthai, M. Mitchai, C. Ratchatane and S. Sima at Khonkhaen Hospital, Thailand; Sasithorn Bejrachandra Siriraj Hospital, Thailand; and M. Callan and P. Klenerman for useful discussion. This work was supported by the Medical Research Council UK (J.M., X.X., T.D., S.R.J., A.M and G.S.), the Senior Research Scholar Program of the Thailand Research Fund (P.M.), a Royal Golden Jubilee Award from the Thailand Research Fund (W.D.) and the Royal Thai Government Doctoral Scholarship (T.D.).
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Mongkolsapaya, J., Dejnirattisai, W., Xu, Xn. et al. Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever. Nat Med 9, 921–927 (2003). https://doi.org/10.1038/nm887
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DOI: https://doi.org/10.1038/nm887
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