{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:29:44Z","timestamp":1791214184485,"version":"4.1.0"},"reference-count":43,"publisher":"Rockefeller University Press","issue":"12","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,6,16]]},"abstract":"<jats:p>Interleukin (IL)-10 is a pleiotropic cytokine which inhibits a broad array of immune parameters including T helper cell type 1 (Th1) cytokine production, antigen presentation, and antigenspecific T cell proliferation. To understand the consequences of altered expression of IL-10 in immune models of autoimmune disease, the response to infectious agents, and the response to tumors, we developed transgenic mice expressing IL-10 under the control of the IL-2 promoter. Upon in vitro stimulation, spleen cells from unimmunized transgenic mice secrete higher levels of IL-10 and lower amounts of IFN-\u03b3 than do controls, although no gross abnormalities were detected in lymphocyte populations or serum Ig levels. Transfer of normally pathogenic CD4+ CD45RBhigh splenic T cells from IL-10 transgenic mice did not cause colitis in recipient severe combined immunodeficiency mice. Furthermore, co-transfer of these transgenic cells with CD4+ CD45RBhigh T cells from control mice prevented disease. Transgenic mice retained their resistance to Leishmania major infection, indicating that their cell-mediated immune responses were not globally suppressed. Lastly, in comparison to controls, IL-10 transgenic mice were unable to limit the growth of immunogenic tumors. Administration of blocking IL-10 mAbs restored in vivo antitumor responses in the transgenic mice. These results demonstrate that a single alteration in the T cell cytokine profile can lead to dramatic changes in immune responses in a manner that is stimulus dependent. These mice will be useful in defining differences in inflammatory conditions and cellular immunity mediated by IL-10.<\/jats:p>","DOI":"10.1084\/jem.185.12.2101","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"2101-2110","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":209,"title":["Altered Immune Responses in Interleukin 10 Transgenic Mice"],"prefix":"10.1084","volume":"185","author":[{"given":"Amy","family":"Hagenbaugh","sequence":"first","affiliation":[{"name":"From the *Molecular Biology Institute, \u2021Department of Microbiology & Immunology, \u00a7Division of Digestive Diseases, and \u2016Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095; \u00b6Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, West Los Angeles Veteran's Administration Medical Center, Los Angeles, California 90073, and University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095; **Department of Medicine and Department of Microbiology & Immunology, University of California at San Francisco, San Francisco, California 94143, \u2020\u2020Midway Hospital Medical Center, Los Angeles, California 90019; and \u00a7\u00a7Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304"},{"name":"From the *Molecular Biology Institute, \u2021Department of Microbiology & Immunology, \u00a7Division of Digestive Diseases, and \u2016Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095; \u00b6Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, West Los Angeles Veteran's Administration Medical Center, Los Angeles, California 90073, and University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095; **Department of Medicine and Department of Microbiology & Immunology, University of California at San Francisco, San Francisco, California 94143, \u2020\u2020Midway Hospital Medical Center, Los Angeles, California 90019; and \u00a7\u00a7Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherven","family":"Sharma","sequence":"additional","affiliation":[{"name":"From the *Molecular Biology Institute, \u2021Department of Microbiology & Immunology, \u00a7Division of Digestive Diseases, and \u2016Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095; \u00b6Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, West Los Angeles Veteran's Administration Medical Center, Los Angeles, California 90073, and University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095; **Department of Medicine and Department of Microbiology & Immunology, University of California at San Francisco, San Francisco, California 94143, \u2020\u2020Midway Hospital Medical Center, Los Angeles, California 90019; and \u00a7\u00a7Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Dubinett","sequence":"additional","affiliation":[{"name":"From the *Molecular Biology Institute, \u2021Department of Microbiology & Immunology, \u00a7Division of Digestive Diseases, and \u2016Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095; \u00b6Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, West Los Angeles Veteran's Administration Medical Center, Los Angeles, California 90073, and University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095; **Department of Medicine and Department of Microbiology & Immunology, University of California at San Francisco, San Francisco, California 94143, \u2020\u2020Midway Hospital Medical Center, Los Angeles, California 90019; and \u00a7\u00a7Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherry H.-Y.","family":"Wei","sequence":"additional","affiliation":[{"name":"From the *Molecular Biology Institute, \u2021Department of Microbiology & Immunology, \u00a7Division of Digestive Diseases, and \u2016Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095; \u00b6Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, West Los Angeles Veteran's Administration Medical Center, Los Angeles, California 90073, and University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095; **Department of Medicine and Department of Microbiology & Immunology, University of California at San Francisco, San Francisco, California 94143, \u2020\u2020Midway Hospital Medical Center, Los Angeles, California 90019; and \u00a7\u00a7Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Aranda","sequence":"additional","affiliation":[{"name":"From the *Molecular Biology Institute, \u2021Department of Microbiology & Immunology, \u00a7Division of Digestive Diseases, and \u2016Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095; \u00b6Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, West Los Angeles Veteran's Administration Medical Center, Los Angeles, California 90073, and University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095; **Department of Medicine and Department of Microbiology & Immunology, University of California at San Francisco, San Francisco, California 94143, \u2020\u2020Midway Hospital Medical Center, Los Angeles, California 90019; and \u00a7\u00a7Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilde","family":"Cheroutre","sequence":"additional","affiliation":[{"name":"From the *Molecular Biology Institute, \u2021Department of Microbiology & Immunology, \u00a7Division of Digestive Diseases, and \u2016Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095; \u00b6Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, West Los Angeles Veteran's Administration Medical Center, Los Angeles, California 90073, and University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095; **Department of Medicine and Department of Microbiology & Immunology, University of California at San Francisco, San Francisco, California 94143, \u2020\u2020Midway Hospital Medical Center, Los Angeles, California 90019; and \u00a7\u00a7Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.","family":"Fowell","sequence":"additional","affiliation":[{"name":"From the *Molecular Biology Institute, \u2021Department of Microbiology & Immunology, \u00a7Division of Digestive Diseases, and \u2016Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095; \u00b6Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, West Los Angeles Veteran's Administration Medical Center, Los Angeles, California 90073, and University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095; **Department of Medicine and Department of Microbiology & Immunology, University of California at San Francisco, San Francisco, California 94143, \u2020\u2020Midway Hospital Medical Center, Los Angeles, California 90019; and \u00a7\u00a7Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Binder","sequence":"additional","affiliation":[{"name":"From the *Molecular Biology Institute, \u2021Department of Microbiology & Immunology, \u00a7Division of Digestive Diseases, and \u2016Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095; \u00b6Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, West Los Angeles Veteran's Administration Medical Center, Los Angeles, California 90073, and University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095; **Department of Medicine and Department of Microbiology & Immunology, University of California at San Francisco, San Francisco, California 94143, \u2020\u2020Midway Hospital Medical Center, Los Angeles, California 90019; and \u00a7\u00a7Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty","family":"Tsao","sequence":"additional","affiliation":[{"name":"From the *Molecular Biology Institute, \u2021Department of Microbiology & Immunology, \u00a7Division of Digestive Diseases, and \u2016Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095; \u00b6Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, West Los Angeles Veteran's Administration Medical Center, Los Angeles, California 90073, and University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095; **Department of Medicine and Department of Microbiology & Immunology, University of California at San Francisco, San Francisco, California 94143, \u2020\u2020Midway Hospital Medical Center, Los Angeles, California 90019; and \u00a7\u00a7Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Locksley","sequence":"additional","affiliation":[{"name":"From the *Molecular Biology Institute, \u2021Department of Microbiology & Immunology, \u00a7Division of Digestive Diseases, and \u2016Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095; \u00b6Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, West Los Angeles Veteran's Administration Medical Center, Los Angeles, California 90073, and University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095; **Department of Medicine and Department of Microbiology & Immunology, University of California at San Francisco, San Francisco, California 94143, \u2020\u2020Midway Hospital Medical Center, Los Angeles, California 90019; and \u00a7\u00a7Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin W.","family":"Moore","sequence":"additional","affiliation":[{"name":"From the *Molecular Biology Institute, \u2021Department of Microbiology & Immunology, \u00a7Division of Digestive Diseases, and \u2016Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095; \u00b6Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, West Los Angeles Veteran's Administration Medical Center, Los Angeles, California 90073, and University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095; **Department of Medicine and Department of Microbiology & Immunology, University of California at San Francisco, San Francisco, California 94143, \u2020\u2020Midway Hospital Medical Center, Los Angeles, California 90019; and \u00a7\u00a7Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell","family":"Kronenberg","sequence":"additional","affiliation":[{"name":"From the *Molecular Biology Institute, \u2021Department of Microbiology & Immunology, \u00a7Division of Digestive Diseases, and \u2016Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095; \u00b6Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, West Los Angeles Veteran's Administration Medical Center, Los Angeles, California 90073, and University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095; **Department of Medicine and Department of Microbiology & Immunology, University of California at San Francisco, San Francisco, California 94143, \u2020\u2020Midway Hospital Medical Center, Los Angeles, California 90019; and \u00a7\u00a7Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304"},{"name":"From the *Molecular Biology Institute, \u2021Department of Microbiology & Immunology, \u00a7Division of Digestive Diseases, and \u2016Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095; \u00b6Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, West Los Angeles Veteran's Administration Medical Center, Los Angeles, California 90073, and University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095; **Department of Medicine and Department of Microbiology & Immunology, University of California at San Francisco, San Francisco, California 94143, \u2020\u2020Midway Hospital Medical Center, Los Angeles, California 90019; and \u00a7\u00a7Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304"},{"name":"From the *Molecular Biology Institute, \u2021Department of Microbiology & Immunology, \u00a7Division of Digestive Diseases, and \u2016Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90095; \u00b6Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, West Los Angeles Veteran's Administration Medical Center, Los Angeles, California 90073, and University of California at Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095; **Department of Medicine and Department of Microbiology & Immunology, University of California at San Francisco, San Francisco, California 94143, \u2020\u2020Midway Hospital Medical Center, Los Angeles, California 90019; and \u00a7\u00a7Department of Molecular Biology, DNAX Research Institute, Palo Alto, California 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1997,6,16]]},"reference":[{"key":"2023072507020583600_B1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/j.1600-065X.1991.tb00612.x","article-title":"Diversity of cytokine synthesis and function of mouse CD4+T cells","volume":"123","author":"Mosmann","year":"1991","journal-title":"Immunol Rev"},{"key":"2023072507020583600_B2","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1084\/jem.170.6.2081","article-title":"Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones","volume":"170","author":"Fiorentino","year":"1989","journal-title":"J Exp Med"},{"key":"2023072507020583600_B3","first-page":"173","article-title":"Interleukin-10 and its receptor","volume":"1","author":"Ho","year":"1994","journal-title":"Ther Immunol"},{"key":"2023072507020583600_B4","doi-asserted-by":"crossref","first-page":"6065","DOI":"10.1073\/pnas.89.13.6065","article-title":"Differential regulation of T helper phenotype development by interleukins 4 and 10 in an \u03b1\u03b2 T-cellreceptor transgenic system","volume":"89","author":"Hsieh","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072507020583600_B5","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.4049\/jimmunol.148.10.3133","article-title":"IL-10 inhibits mitogeninduced T cell proliferation by selectively inhibiting macrophage costimulatory function","volume":"148","author":"Ding","year":"1992","journal-title":"J Immunol"},{"key":"2023072507020583600_B6","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.4049\/jimmunol.151.3.1224","article-title":"IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression","volume":"151","author":"Ding","year":"1993","journal-title":"J Immunol"},{"key":"2023072507020583600_B7","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.4049\/jimmunol.147.11.3815","article-title":"IL-10 inhibits cytokine production by activated macrophages","volume":"147","author":"Fiorentino","year":"1991","journal-title":"J Immunol"},{"key":"2023072507020583600_B8","doi-asserted-by":"crossref","first-page":"3444","DOI":"10.4049\/jimmunol.146.10.3444","article-title":"IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells","volume":"146","author":"Fiorentino","year":"1991","journal-title":"J Immunol"},{"key":"2023072507020583600_B9","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1146\/annurev.iy.11.040193.001121","article-title":"Interleukin-10","volume":"11","author":"Moore","year":"1993","journal-title":"Annu Rev Immunol"},{"key":"2023072507020583600_B10","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.4049\/jimmunol.148.11.3618","article-title":"Structure of the mouse IL-10 gene and chromosomal localization of the mouse and human genes","volume":"148","author":"Kim","year":"1992","journal-title":"J Immunol"},{"key":"2023072507020583600_B11","doi-asserted-by":"crossref","first-page":"350","DOI":"10.4049\/jimmunol.149.1.350","article-title":"Failed self-tolerance and autoimmunity in IgG anti-DNA transgenic mice","volume":"149","author":"Tsao","year":"1992","journal-title":"J Immunol"},{"key":"2023072507020583600_B12","doi-asserted-by":"crossref","first-page":"3464","DOI":"10.4049\/jimmunol.158.7.3464","article-title":"Analysis of intestinal lymphocytes in mouse colitis mediated by transfer of CD4+, CD45RBhighT cells to SCID recipients","volume":"158","author":"Aranda","year":"1997","journal-title":"J Immunol"},{"key":"2023072507020583600_B13","doi-asserted-by":"crossref","first-page":"4142","DOI":"10.4049\/jimmunol.153.9.4142","article-title":"Differential effects of blockade of CD28-B7 on the development of Th1 or Th2 effector cells in experimental leishmaniasis","volume":"153","author":"Corry","year":"1994","journal-title":"J Immunol"},{"key":"2023072507020583600_B14","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1084\/jem.179.4.1367","article-title":"CD4+ effector cells default to the Th2 pathway in interferon \u03b3-deficient mice infected with Leishmania major.","volume":"179","author":"Wang","year":"1994","journal-title":"J Exp Med"},{"key":"2023072507020583600_B15","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev.iy.12.040194.003223","article-title":"Acquisition of lymphokine-producing phenotype by CD4+ T cells","volume":"12","author":"Seder","year":"1994","journal-title":"Annu Rev Immunol"},{"key":"2023072507020583600_B16","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1084\/jem.177.5.1451","article-title":"The selective ablation of interleukin 2\u2013producing cells isolated from transgenic mice","volume":"177","author":"Minasi","year":"1993","journal-title":"J Exp Med"},{"key":"2023072507020583600_B17","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1126\/science.2595372","article-title":"Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation","volume":"246","author":"Emmel","year":"1989","journal-title":"Science (Wash DC)"},{"key":"2023072507020583600_B18","doi-asserted-by":"crossref","first-page":"15788","DOI":"10.1016\/S0021-9258(18)55467-3","article-title":"Cell type specificity and activation requirements for NFAT-1 (nuclear factor of activated T-cells) transcriptional activity determined by a new method using transgenic mice to assay transcriptional activity of an individual nuclear factor","volume":"265","author":"Verweij","year":"1990","journal-title":"J Biol Chem"},{"key":"2023072507020583600_B19","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1093\/intimm\/6.2.189","article-title":"IL-2 promoterdriven lacZ expression as a monitoring tool for IL-2 expression in primary T cells of transgenic mice","volume":"6","author":"Brombacher","year":"1994","journal-title":"Int Immunol"},{"key":"2023072507020583600_B20","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1093\/intimm\/5.11.1461","article-title":"Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scidmice","volume":"5","author":"Powrie","year":"1993","journal-title":"Int Immunol"},{"key":"2023072507020583600_B21","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/1074-7613(94)90045-0","article-title":"Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+T cells","volume":"1","author":"Powrie","year":"1994","journal-title":"Immunity"},{"key":"2023072507020583600_B22","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1084\/jem.179.2.589","article-title":"Regulatory interactions between CD45RBhigh and CD45RBlow CD4+T cells are important for the balance between protective and pathogenic cell-mediated immunity","volume":"179","author":"Powrie","year":"1994","journal-title":"J Exp Med"},{"key":"2023072507020583600_B23","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1084\/jem.178.1.237","article-title":"CD4+ T cells that express high levels of CD45RB induce wasting disease when transferred into congenic severe combined immunodeficient mice. 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