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

Abstract
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.
AuthorsDavid G Brooks, Andrew M Lee, Heidi Elsaesser, Dorian B McGavern, Michael B A Oldstone
JournalThe Journal of experimental medicine (J Exp Med) Vol. 205 Issue 3 Pg. 533-41 (Mar 17 2008) ISSN: 1540-9538 [Electronic] United States
PMID18332180 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Receptors, Interleukin-10
  • Vaccines, DNA
  • Viral Vaccines
  • Interleukin-10
Topics
  • Animals
  • Arenaviridae Infections (immunology, virology)
  • Immunosuppression Therapy
  • Interleukin-10 (antagonists & inhibitors)
  • Lymphocytic choriomeningitis virus (genetics, immunology)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Interleukin-10 (antagonists & inhibitors)
  • T-Lymphocytes (immunology, virology)
  • Vaccination
  • Vaccines, DNA (genetics, pharmacology)
  • Viral Vaccines (genetics, pharmacology)

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