The Journal of Experimental Medicine
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Published online March 10, 2008
doi:10.1084/jem.20071948
The Journal of Experimental Medicine, Vol. 205, No. 3, 533-541
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Brooks et al.
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BRIEF DEFINITIVE REPORT

 IL-10 blockade facilitates DNA vaccine-induced T cell responses and enhances clearance of persistent virus infection

David G. Brooks1, Andrew M. Lee1, Heidi Elsaesser1, Dorian B. McGavern1, and Michael B.A. Oldstone1,2

1 Viral-Immunobiology Laboratory, Department of Molecular and Integrative Neuroscience, and 2 Department of Infectology, The Scripps Research Institute, La Jolla, CA 92037

CORRESPONDENCE David G. Brooks: dbrooks{at}scripps.edu

Therapeutic vaccination is a potentially powerful strategy to establish immune control and eradicate persistent viral infections. Large and multifunctional antiviral T cell responses are associated with control of viral persistence; however, for reasons that were mostly unclear, current therapeutic vaccination approaches to restore T cell immunity and control viral infection have been ineffective. Herein, we confirmed that neutralization of the immunosuppressive factor interleukin (IL)-10 stimulated T cell responses and improved control of established persistent lymphocytic choriomeningitis virus (LCMV) infection. Importantly, blockade of IL-10 also allowed an otherwise ineffective therapeutic DNA vaccine to further stimulate antiviral immunity, thereby increasing T cell responses and enhancing clearance of persistent LCMV replication. We therefore propose that a reason that current therapeutic vaccination strategies fail to resurrect/sustain T cell responses is because they do not alleviate the immunosuppressive environment. Consequently, blocking key suppressive factors could render ineffective vaccines more efficient at improving T cell immunity, and thereby allow immune-mediated control of persistent viral infection.


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