Home | Help | Feedback | Subscriptions | Archive | Search | Latest Articles

This Article Full Text Full Text (PDF, 1260K) PPT slides of all figures 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 Ejrnaes, M. Articles by von Herrath, M. G. Search for Related Content PubMed PubMed Citation Articles by Ejrnaes, M. Articles by von Herrath, M. G. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Related Collections Related Article Social Bookmarking                            What's this?

ARTICLE

¹ Immune Regulation Lab – DI3 and ² Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037

CORRESPONDENCE Matthias G. von Herrath: matthias{at}liai.org

A defining characteristic of persistent viral infections is the loss and functional inactivation of antiviral effector T cells, which prevents viral clearance. Interleukin-10 (IL-10) suppresses cellular immune responses by modulating the function of T cells and antigen-presenting cells. In this paper, we report that IL-10 production is drastically increased in mice persistently infected with lymphocytic choriomeningitis virus. In vivo blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulted in rapid resolution of the persistent infection. IL-10 secretion was diminished and interferon production by antiviral CD8⁺ T cells was enhanced. In persistently infected mice, CD8⁺ dendritic cell (DC) numbers declined early after infection, whereas CD8^– DC numbers were not affected. CD8^– DCs supported IL-10 production and subsequent dampening of antiviral T cell responses. Therapeutic IL-10R blockade broke the cycle of IL-10–mediated immune suppression, preventing IL-10 priming by CD8^– DCs and enhancing antiviral responses and thereby resolving infection without causing immunopathology.

M. Ejrnaes, C.M. Filippi, and M.M. Martinic contributed equally to this paper.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

Curtailing infection

Ruth Williams
J. Exp. Med. 2006 203: 2393. [Full Text] [PDF]

This article has been cited by other articles:

• Richter, K., Agnellini, P., Oxenius, A. (2009). On the role of the inhibitory receptor LAG-3 in acute and chronic LCMV infection. Int Immunol 0: dxp107v1-dxp107 [Abstract] [Full Text]  
• Lee, S.-H., Kim, K.-S., Fodil-Cornu, N., Vidal, S. M., Biron, C. A. (2009). Activating receptors promote NK cell expansion for maintenance, IL-10 production, and CD8 T cell regulation during viral infection. JEM 206: 2235-2251 [Abstract] [Full Text]  
• Sarasin-Filipowicz, M., Wang, X., Yan, M., Duong, F. H. T., Poli, V., Hilton, D. J., Zhang, D.-E., Heim, M. H. (2009). Alpha Interferon Induces Long-Lasting Refractoriness of JAK-STAT Signaling in the Mouse Liver through Induction of USP18/UBP43. Mol. Cell. Biol. 29: 4841-4851 [Abstract] [Full Text]  
• Madan, R., Demircik, F., Surianarayanan, S., Allen, J. L., Divanovic, S., Trompette, A., Yogev, N., Gu, Y., Khodoun, M., Hildeman, D., Boespflug, N., Fogolin, M. B., Grobe, L., Greweling, M., Finkelman, F. D., Cardin, R., Mohrs, M., Muller, W., Waisman, A., Roers, A., Karp, C. L. (2009). Nonredundant Roles for B Cell-Derived IL-10 in Immune Counter-Regulation. J. Immunol. 183: 2312-2320 [Abstract] [Full Text]  
• Aleyas, A. G., George, J. A., Han, Y. W., Rahman, M. M., Kim, S. J., Han, S. B., Kim, B. S., Kim, K., Eo, S. K. (2009). Functional Modulation of Dendritic Cells and Macrophages by Japanese Encephalitis Virus through MyD88 Adaptor Molecule-Dependent and -Independent Pathways. J. Immunol. 183: 2462-2474 [Abstract] [Full Text]  
• Brooks, D. G. (2009). Suppressing the suppressor. Blood 114: 233-233 [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]  
• Elsaesser, H., Sauer, K., Brooks, D. G. (2009). IL-21 Is Required to Control Chronic Viral Infection. Science 324: 1569-1572 [Abstract] [Full Text]  
• Frohlich, A., Kisielow, J., Schmitz, I., Freigang, S., Shamshiev, A. T., Weber, J., Marsland, B. J., Oxenius, A., Kopf, M. (2009). IL-21R on T Cells Is Critical for Sustained Functionality and Control of Chronic Viral Infection. Science 324: 1576-1580 [Abstract] [Full Text]  
• McKinstry, K. K., Strutt, T. M., Buck, A., Curtis, J. D., Dibble, J. P., Huston, G., Tighe, M., Hamada, H., Sell, S., Dutton, R. W., Swain, S. L. (2009). IL-10 Deficiency Unleashes an Influenza-Specific Th17 Response and Enhances Survival against High-Dose Challenge. J. Immunol. 182: 7353-7363 [Abstract] [Full Text]  
• Blattman, J. N., Wherry, E. J., Ha, S.-J., van der Most, R. G., Ahmed, R. (2009). Impact of Epitope Escape on PD-1 Expression and CD8 T-Cell Exhaustion during Chronic Infection. J. Virol. 83: 4386-4394 [Abstract] [Full Text]  
• van Gisbergen, K. P. J. M., van Olffen, R. W., van Beek, J., van der Sluijs, K. F., Arens, R., Nolte, M. A., van Lier, R. A. (2009). Protective CD8 T Cell Memory Is Impaired during Chronic CD70-Driven Costimulation. J. Immunol. 182: 5352-5362 [Abstract] [Full Text]  
• Stacey, A. R., Norris, P. J., Qin, L., Haygreen, E. A., Taylor, E., Heitman, J., Lebedeva, M., DeCamp, A., Li, D., Grove, D., Self, S. G., Borrow, P. (2009). Induction of a Striking Systemic Cytokine Cascade prior to Peak Viremia in Acute Human Immunodeficiency Virus Type 1 Infection, in Contrast to More Modest and Delayed Responses in Acute Hepatitis B and C Virus Infections. J. Virol. 83: 3719-3733 [Abstract] [Full Text]  
• Bamboat, Z. M., Stableford, J. A., Plitas, G., Burt, B. M., Nguyen, H. M., Welles, A. P., Gonen, M., Young, J. W., DeMatteo, R. P. (2009). Human Liver Dendritic Cells Promote T Cell Hyporesponsiveness. J. Immunol. 182: 1901-1911 [Abstract] [Full Text]  
• Endoh, Y., Chung, Y. M., Clark, I. A., Geczy, C. L., Hsu, K. (2009). IL-10-Dependent S100A8 Gene Induction in Monocytes/Macrophages by Double-Stranded RNA. J. Immunol. 182: 2258-2268 [Abstract] [Full Text]  
• Liu, B., Woltman, A. M., Janssen, H. L. A., Boonstra, A. (2009). Modulation of dendritic cell function by persistent viruses. J. Leukoc. Biol. 85: 205-214 [Abstract] [Full Text]  
• Baenziger, S., Heikenwalder, M., Johansen, P., Schlaepfer, E., Hofer, U., Miller, R. C., Diemand, S., Honda, K., Kundig, T. M., Aguzzi, A., Speck, R. F. (2009). Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology. Blood 113: 377-388 [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]  
• Filippi, C. M., von Herrath, M. G. (2008). Viral Trigger for Type 1 Diabetes: Pros and Cons. Diabetes 57: 2863-2871 [Full Text]  
• Walker, B. D., Burton, D. R. (2008). Toward an AIDS Vaccine. Science 320: 760-764 [Abstract] [Full Text]  
• Couper, K. N., Blount, D. G., Riley, E. M. (2008). IL-10: The Master Regulator of Immunity to Infection. J. Immunol. 180: 5771-5777 [Abstract] [Full Text]  
• Plesa, G., Snook, A. E., Waldman, S. A., Eisenlohr, L. C. (2008). Derivation and Fluidity of Acutely Induced Dysfunctional CD8+ T Cells. J. Immunol. 180: 5300-5308 [Abstract] [Full Text]  
• Lukens, J. R., Cruise, M. W., Lassen, M. G., Hahn, Y. S. (2008). Blockade of PD-1/B7-H1 Interaction Restores Effector CD8+ T Cell Responses in a Hepatitis C Virus Core Murine Model. J. Immunol. 180: 4875-4884 [Abstract] [Full Text]  
• Brooks, D. G., Lee, A. M., Elsaesser, H., McGavern, D. B., Oldstone, M. B.A. (2008). IL-10 blockade facilitates DNA vaccine-induced T cell responses and enhances clearance of persistent virus infection. JEM 205: 533-541 [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]  
• Green, K. A., Okazaki, T., Honjo, T., Cook, W. J., Green, W. R. (2008). The Programmed Death-1 and Interleukin-10 Pathways Play a Down-Modulatory Role in LP-BM5 Retrovirus-Induced Murine Immunodeficiency Syndrome. J. Virol. 82: 2456-2469 [Abstract] [Full Text]  
• Tu, Z., Bozorgzadeh, A., Pierce, R. H., Kurtis, J., Crispe, I. N., Orloff, M. S. (2008). TLR-dependent cross talk between human Kupffer cells and NK cells. JEM 205: 233-244 [Abstract] [Full Text]  
• Robertson, S. J., Ammann, C. G., Messer, R. J., Carmody, A. B., Myers, L., Dittmer, U., Nair, S., Gerlach, N., Evans, L. H., Cafruny, W. A., Hasenkrug, K. J. (2008). Suppression of Acute Anti-Friend Virus CD8+ T-Cell Responses by Coinfection with Lactate Dehydrogenase-Elevating Virus. J. Virol. 82: 408-418 [Abstract] [Full Text]  
• Biswas, P. S., Pedicord, V., Ploss, A., Menet, E., Leiner, I., Pamer, E. G. (2007). Pathogen-Specific CD8 T Cell Responses Are Directly Inhibited by IL-10. J. Immunol. 179: 4520-4528 [Abstract] [Full Text]  
• Brignone, C., Grygar, C., Marcu, M., Schakel, K., Triebel, F. (2007). A Soluble Form of Lymphocyte Activation Gene-3 (IMP321) Induces Activation of a Large Range of Human Effector Cytotoxic Cells. J. Immunol. 179: 4202-4211 [Abstract] [Full Text]  
• Althaus, C. L., Ganusov, V. V., De Boer, R. J. (2007). Dynamics of CD8+ T Cell Responses during Acute and Chronic Lymphocytic Choriomeningitis Virus Infection. J. Immunol. 179: 2944-2951 [Abstract] [Full Text]  
• Billerbeck, E., Blum, H. E., Thimme, R. (2007). Parallel Expansion of Human Virus-Specific FoxP3- Effector Memory and De Novo-Generated FoxP3+ Regulatory CD8+ T Cells upon Antigen Recognition In Vitro. J. Immunol. 179: 1039-1048 [Abstract] [Full Text]  
• Mothe, B. R., Stewart, B. S., Oseroff, C., Bui, H.-H., Stogiera, S., Garcia, Z., Dow, C., Rodriguez-Carreno, M. P., Kotturi, M., Pasquetto, V., Botten, J., Crotty, S., Janssen, E., Buchmeier, M. J., Sette, A. (2007). Chronic Lymphocytic Choriomeningitis Virus Infection Actively Down-Regulates CD4+ T Cell Responses Directed against a Broad Range of Epitopes. J. Immunol. 179: 1058-1067 [Abstract] [Full Text]  
• Andrews, N. P., Pack, C. D., Vezys, V., Barber, G. N., Lukacher, A. E. (2007). Early Virus-Associated Bystander Events Affect the Fitness of the CD8 T Cell Response to Persistent Virus Infection. J. Immunol. 178: 7267-7275 [Abstract] [Full Text]  
• Humphreys, I. R., de Trez, C., Kinkade, A., Benedict, C. A., Croft, M., Ware, C. F. (2007). Cytomegalovirus exploits IL-10-mediated immune regulation in the salivary glands. JEM 204: 1217-1225 [Abstract] [Full Text]  
• den Haan, J. M. M., Kraal, G., Bevan, M. J. (2007). Cutting Edge: Lipopolysaccharide Induces IL-10-Producing Regulatory CD4+ T Cells That Suppress the CD8+ T Cell Response. J. Immunol. 178: 5429-5433 [Abstract] [Full Text]  
• Agnellini, P., Wolint, P., Rehr, M., Cahenzli, J., Karrer, U., Oxenius, A. (2007). Impaired NFAT nuclear translocation results in split exhaustion of virus-specific CD8+ T cell functions during chronic viral infection. Proc. Natl. Acad. Sci. USA 104: 4565-4570 [Abstract] [Full Text]  
• Trinchieri, G. (2007). Interleukin-10 production by effector T cells: Th1 cells show self control. JEM 204: 239-243 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search