Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 205, Issue 3, Pages 533-541Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20071948
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Funding
- NIAID NIH HHS [AI062718-01, AI45927, R01 AI045927, AI09484, T32 AI007244, R21 AI077012, R01 AI009484, AI077012-01, AI07244-22, R21 AI062718] Funding Source: Medline
- NINDS NIH HHS [NS048866-01, R21 NS048866] Funding Source: Medline
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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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