IMMUNOPATHOLOGIC MECHANISMS OF DENGUE HEMORRHAGIC-FEVER AND DENGUE SHOCK SYNDROME

Dengue virus infections are a major cause of morbidity and mortality i n tropical and subtropical areas of the world. The immunopathological mechanisms that result in severe complications of dengue virus infecti on, i.e. dengue hemorrhagic fever (DHF), are important to determine. P rimary dengue virus infections induce serotype-specific and serotype-c ross-reactive, CD4+ and CD8+ memory cytotoxic T lymphocytes (CTL). In secondary infections with a virus of a different serotype from that wh ich caused primary infections, the presence of cross-reactive non-neut ralizing antibodies results in an increased number of infected monocyt es by dengue virus - antibody complexes. This in turn results in marke d activation of serotype cross-reactive CD4+ and CD8+ memory CTL. We h ypothesize that the rapid release of cytokines and chemical mediators caused by T cell activation and by CTL-mediated lysis of dengue virus- infected monocytes triggers the plasma leakage and hemorrhage that occ urs in DHF.