Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 2003K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Brooks, D. G. Articles by Oldstone, M. B.A. Search for Related Content PubMed PubMed Citation Articles by Brooks, D. G. Articles by Oldstone, M. B.A. Related Collections Related Article Social Bookmarking                            What's this?

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.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Facebook

Reddit

Technorati

Twitter

This article has been cited by other articles:

• Takagi, A., Matsui, M., Ohno, S., Duan, H., Moriya, O., Kobayashi, N., Oda, H., Mori, M., Kobayashi, A., Taneichi, M., Uchida, T., Akatsuka, T. (2009). Highly Efficient Antiviral CD8+ T-Cell Induction by Peptides Coupled to the Surfaces of Liposomes. CVI 16: 1383-1392 [Abstract] [Full Text]  
• Brockman, M. A., Kwon, D. S., Tighe, D. P., Pavlik, D. F., Rosato, P. C., Sela, J., Porichis, F., Le Gall, S., Waring, M. T., Moss, K., Jessen, H., Pereyra, F., Kavanagh, D. G., Walker, B. D., Kaufmann, D. E. (2009). IL-10 is up-regulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells. Blood 114: 346-356 [Abstract] [Full Text]  
• Chang, D.-Y., Shin, E.-C. (2009). Immune-based therapy for chronic hepatitis C. J. Leukoc. Biol. 86: 33-39 [Abstract] [Full Text]  
• Liu, X. S., Leerberg, J., MacDonald, K., Leggatt, G. R., Frazer, I. H. (2009). IFN-{gamma} Promotes Generation of IL-10 Secreting CD4+ T Cells that Suppress Generation of CD8 Responses in an Antigen-Experienced Host. J. Immunol. 183: 51-58 [Abstract] [Full Text]  
• Kaufmann, D. E., Walker, B. D. (2009). PD-1 and CTLA-4 Inhibitory Cosignaling Pathways in HIV Infection and the Potential for Therapeutic Intervention. J. Immunol. 182: 5891-5897 [Abstract] [Full Text]  
• Brooks, D. G., Ha, S.-J., Elsaesser, H., Sharpe, A. H., Freeman, G. J., Oldstone, M. B. A. (2008). IL-10 and PD-L1 operate through distinct pathways to suppress T-cell activity during persistent viral infection. Proc. Natl. Acad. Sci. USA 105: 20428-20433 [Abstract] [Full Text]  
• Ha, S.-J., Mueller, S. N., Wherry, E. J., Barber, D. L., Aubert, R. D., Sharpe, A. H., Freeman, G. J., Ahmed, R. (2008). Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals during chronic infection. JEM 205: 543-555 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS