Published online
doi:10.1084/jem.20082030
The Journal of Experimental Medicine, Vol. 206, No. 2, 313-328
The Rockefeller University Press, 0022-1007 $30.00
© Hou et al.
Th17 cells enhance viral persistence and inhibit T cell cytotoxicity in a model of chronic virus infection
Wanqiu Hou,
Hyun Seok Kang, and
Byung S. Kim
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611
CORRESPONDENCE Byung S. Kim: bskim{at}northwestern.edu
Persistent viral infection and its associated chronic diseases are a global health concern. Interleukin (IL) 17–producing Th17 cells have been implicated in the pathogenesis of various autoimmune diseases, and in protection from bacterial or fungal infection. However, the role of Th17 cells in persistent viral infection remains unknown. We report that Th17 cells preferentially develop in vitro and in vivo in an IL-6–dependent manner after Theiler’s murine encephalomyelitis virus infection. Th17 cells promote persistent viral infection and induce the pathogenesis of chronic demyelinating disease. IL-17 up-regulates antiapoptotic molecules and, consequently, increases persistent infection by enhancing the survival of virus-infected cells and blocking target cell destruction by cytotoxic T cells. Neutralization of IL-17 augments virus clearance by eliminating virus-infected cells and boosting lytic function by cytotoxic T cells, leading to the prevention of disease development. Thus, these results indicate a novel pathogenic role of Th17 cells via IL-17 in persistent viral infection and its associated chronic inflammatory diseases.
Abbreviations used: Bcl, B cell lymphoma; BMDC, BM-derived DC; CNS, central nervous system; MOI, multiplicity of infection; TMEV, Theiler’s murine encephalomyelitis virus; UV-TMEV, UV light–inactivated TMEV.
© 2009 Hou et al.
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