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Journal of Virology, May 1999, p. 3623-3629, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Bystander Target Cell Lysis and Cytokine Production by Dengue Virus-Specific Human CD4+ Cytotoxic T-Lymphocyte Clones

Susan J. Gagnon, Francis A. Ennis, and Alan L. Rothman*

Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical Center, Worcester, Massachusetts 01655

Received 17 July 1998/Accepted 19 January 1999

Dengue 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.

* Corresponding author. Mailing address: Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical Center, 55 Lake Ave. North, Worcester, MA 01655. Phone: (508) 856-4182. Fax: (508) 856-4890. E-mail: Alan.Rothman{at}umassmed.edu.

Journal of Virology, May 1999, p. 3623-3629, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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