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DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304
IL-10 is a cytokine secreted by a wide variety of cells type that has pleiotropic stimulatory and suppressive activities on both lymphoid and myeloid cells in vitro. To analyze the consequences of high IL-10 secretion by APCs in immune responses, we produced transgenic mice expressing human IL-10 directed by the MHC class II Ea promoter. Despite alterations in the development of T and B cells, no gross abnormalities were detected in peripheral lymphocyte populations or serum Ig levels. However, when immunized using conditions that give either a Th2-type or a Th1-type response, IL-10 transgenic mice failed to mount a significant T or B cell immune response to OVA. IL-10 transgenic mice were also highly susceptible to infection with intracellular pathogens like Listeria monocytogenes or Leishmania major, in contrast to IL-10 transgenic mice, where the transgene was express in T cells. Finally, the recently described stimulatory effect of IL-10 on CD8+ T cells was confirmed by the ability of IL-10 transgenic mice to limit the growth of immunogenic tumors by a CTL-mediated mechanism. These results demonstrate, that, depending on the type of immune response, IL-10 can mediate immunosuppressive or immunostimulatory activities in vivo.
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Y. Belkaid, K. F. Hoffmann, S. Mendez, S. Kamhawi, M. C. Udey, T. A. Wynn, and D. L. Sacks The Role of Interleukin (IL)-10 in the Persistence of Leishmania major in the Skin after Healing and the Therapeutic Potential of Anti-IL-10 Receptor Antibody for Sterile Cure J. Exp. Med., November 19, 2001; 194(10): 1497 - 1506. [Abstract] [Full Text] [PDF]
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S.-i. Fujii, K. Shimizu, T. Shimizu, and M. T. Lotze Interleukin-10 promotes the maintenance of antitumor CD8+ T-cell effector function in situ Blood, October 1, 2001; 98(7): 2143 - 2151. [Abstract] [Full Text] [PDF]
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V. Dheenadhayalan, S. Shanmugalakshmi, S. Vani, P. Muthuveeralakshmi, G. Arivarignan, A. D. Nageswari, and R M. Pitchappan Association of Interleukin-10 Cytokine Expression Status with HLA Non-DRB1*02 and Mycobacterium bovis BCG Scar-Negative Status in South Indian Pulmonary Tuberculosis Patients Infect. Immun., September 1, 2001; 69(9): 5635 - 5642. [Abstract] [Full Text] [PDF]
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S. Kawamoto, Y. Nitta, F. Tashiro, A. Nakano, E. Yamato, H. Tahara, K. Tabayashi, and J.-i. Miyazaki Suppression of Th1 cell activation and prevention of autoimmune diabetes in NOD mice by local expression of viral IL-10 Int. Immunol., May 1, 2001; 13(5): 685 - 694. [Abstract] [Full Text] [PDF]
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S. Corinti, C. Albanesi, A. la Sala, S. Pastore, and G. Girolomoni Regulatory Activity of Autocrine IL-10 on Dendritic Cell Functions J. Immunol., April 1, 2001; 166(7): 4312 - 4318. [Abstract] [Full Text] [PDF]
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S. Bhattacharyya, S. Ghosh, P. L. Jhonson, S. K. Bhattacharya, and S. Majumdar Immunomodulatory Role of Interleukin-10 in Visceral Leishmaniasis: Defective Activation of Protein Kinase C-Mediated Signal Transduction Events Infect. Immun., March 1, 2001; 69(3): 1499 - 1507. [Abstract] [Full Text] [PDF]
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M. T. Liu, D. Armstrong, T. A. Hamilton, and T. E. Lane Expression of Mig (Monokine Induced by Interferon-{{gamma}}) Is Important in T Lymphocyte Recruitment and Host Defense Following Viral Infection of the Central Nervous System J. Immunol., February 1, 2001; 166(3): 1790 - 1795. [Abstract] [Full Text] [PDF]
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M. M. Kane and D. M. Mosser The Role of IL-10 in Promoting Disease Progression in Leishmaniasis J. Immunol., January 15, 2001; 166(2): 1141 - 1147. [Abstract] [Full Text] [PDF]
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B. Balasa, A. La Cava, K. Van Gunst, L. Mocnik, D. Balakrishna, N. Nguyen, L. Tucker, and N. Sarvetnick A Mechanism for IL-10-Mediated Diabetes in the Nonobese Diabetic (NOD) Mouse: ICAM-1 Deficiency Blocks Accelerated Diabetes J. Immunol., December 15, 2000; 165(12): 7330 - 7337. [Abstract] [Full Text] [PDF]
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A. G.S. van Halteren, B. Mosselman, B. O. Roep, W. van Eden, A. Cooke, G. Kraal, and M. H. M. Wauben T Cell Reactivity to Heat Shock Protein 60 in Diabetes-Susceptible and Genetically Protected Nonobese Diabetic Mice Is Associated with a Protective Cytokine Profile J. Immunol., November 15, 2000; 165(10): 5544 - 5551. [Abstract] [Full Text] [PDF]
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I. V. Lyadova, E. B. Eruslanov, S. V. Khaidukov, V. V. Yeremeev, K. B. Majorov, A. V. Pichugin, B. V. Nikonenko, T. K. Kondratieva, and A. S. Apt Comparative Analysis of T Lymphocytes Recovered from the Lungs of Mice Genetically Susceptible, Resistant, and Hyperresistant to Mycobacterium tuberculosis-Triggered Disease J. Immunol., November 15, 2000; 165(10): 5921 - 5931. [Abstract] [Full Text] [PDF]
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F. N. Lauw, D. Pajkrt, C. E. Hack, M. Kurimoto, S. J. H. van Deventer, and T. van der Poll Proinflammatory Effects of IL-10 During Human Endotoxemia J. Immunol., September 1, 2000; 165(5): 2783 - 2789. [Abstract] [Full Text] [PDF]
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B. Balasa, K. Van Gunst, N. Jung, D. Balakrishna, P. Santamaria, T. Hanafusa, N. Itoh, and N. Sarvetnick Islet-Specific Expression of IL-10 Promotes Diabetes in Nonobese Diabetic Mice Independent of Fas, Perforin, TNF Receptor-1, and TNF Receptor-2 Molecules J. Immunol., September 1, 2000; 165(5): 2841 - 2849. [Abstract] [Full Text] [PDF]
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Y. Belkaid, S. Mendez, R. Lira, N. Kadambi, G. Milon, and D. Sacks A Natural Model of Leishmania major Infection Reveals a Prolonged ""Silent"" Phase of Parasite Amplification in the Skin Before the Onset of Lesion Formation and Immunity J. Immunol., July 15, 2000; 165(2): 969 - 977. [Abstract] [Full Text] [PDF]
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H. D. Brightbill, S. E. Plevy, R. L. Modlin, and S. T. Smale A Prominent Role for Sp1 During Lipopolysaccharide- Mediated Induction of the IL-10 Promoter in Macrophages J. Immunol., February 15, 2000; 164(4): 1940 - 1951. [Abstract] [Full Text] [PDF]
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L. Li, M. Crowley, A. Nguyen, and D. Lo Ability of a Nondepleting Anti-CD4 Antibody to Inhibit Th2 Responses and Allergic Lung Inflammation Is Independent of Coreceptor Function J. Immunol., December 15, 1999; 163(12): 6557 - 6566. [Abstract] [Full Text] [PDF]
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 M. R. Stämpfli, M. Cwiartka, B. U. Gajewska, D. Alvarez, S. A. Ritz, M. D. Inman, Z. Xing, and M. Jordana Interleukin-10 Gene Transfer to the Airway Regulates Allergic Mucosal Sensitization in Mice Am. J. Respir. Cell Mol. Biol., November 1, 1999; 21(5): 586 - 596. [Abstract] [Full Text]
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S. Sharma, M. Stolina, Y. Lin, B. Gardner, P. W. Miller, M. Kronenberg, and S. M. Dubinett T Cell-Derived IL-10 Promotes Lung Cancer Growth by Suppressing Both T Cell and APC Function J. Immunol., November 1, 1999; 163(9): 5020 - 5028. [Abstract] [Full Text] [PDF]
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D. J. Cua, H. Groux, D. R. Hinton, S. A. Stohlman, and R. L. Coffman Transgenic Interleukin 10 Prevents Induction of Experimental Autoimmune Encephalomyelitis J. Exp. Med., March 15, 1999; 189(6): 1005 - 1010. [Abstract] [Full Text] [PDF]
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