Dengue fever is caused by an arthropod-borne flavivirus and usually presents as a self-limiting febrile illness, but in more severe cases, a high fever, hemorrhaging, and plasma leakage can occur. There are many cases of dengue fever each year, and the development of an effective dengue vaccine is hampered by a lack of understanding of the precise role of immune cells in dengue fever. In the June 15 Nature Medicine, Juthathip Mongkolsapaya and colleagues at the John Radcliffe Hospital show that profound T-cell activation and death may contribute to the systemic disturbances leading to dengue fever, and original antigenic sin in the T-cell responses may suppress or delay viral elimination, leading to higher viral loads and increased immunopathology (Nature Medicine, DOI:10.1038/nm887, June 15, 2003).