Bystander target cell lysis and cytokine production by dengue virus-specific human CD4(+) cytotoxic T-lymphocyte clones
UMass Chan AffiliationsCenter for Infectious Disease and Vaccine Research
Graduate School of Biomedical Sciences
KeywordsAntigen Presentation; Antigens, CD95; CD4-Positive T-Lymphocytes; Cytotoxicity, Immunologic; Dengue Virus; Fas Ligand Protein; Humans; Interferon Type II; Lymphocyte Activation; Lymphotoxin-alpha; Membrane Glycoproteins; T-Lymphocytes, Cytotoxic; Tumor Necrosis Factor-alpha
Medicine and Health Sciences
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AbstractDengue hemorrhagic fever, the severe form of dengue virus infection, is believed to be an immunopathological response to a secondary infection with a heterologous serotype of dengue virus. Dengue virus capsid protein-specific CD4(+) cytotoxic T-lymphocyte (CTL) clones were shown to be capable of mediating bystander lysis of non-antigen-presenting target cells. After activation by anti-CD3 or in the presence of unlabeled antigen-presenting target cells, these clones could lyse both Jurkat cells and HepG2 cells as bystander targets. Lysis of HepG2 cells suggests a potential role for CD4(+) CTL in the liver involvement observed during dengue virus infection. Three CD4(+) CTL clones were demonstrated to lyse cognate, antigen-presenting target cells by a mechanism that primarily involves perforin, while bystander lysis occurred through Fas/Fas ligand interactions. In contrast, one clone used a Fas/Fas ligand mechanism to lyse both cognate and bystander targets. Cytokine production by the CTL clones was also examined. In response to stimulation with D2 antigen, CD4(+) T-cell clones produced gamma interferon, tumor necrosis factor alpha (TNF-alpha) and TNF-beta. The data suggest that CD4(+) CTL clones may contribute to the immunopathology observed upon secondary dengue virus infections through direct cytolysis and/or cytokine production.
J Virol. 1999 May;73(5):3623-9.