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Altered immune responses in interleukin 10 transgenic mice.

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 antigen-specific 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-gamma 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.

Pubmed ID: 9182682 RIS Download

Mesh terms: Animals | Cells, Cultured | Colitis | Female | Immunity | Interleukin-10 | Leishmaniasis, Cutaneous | Lung Neoplasms | Lymphocytes | Male | Mice | Mice, Inbred C3H | Mice, Inbred C57BL | Mice, Transgenic

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Associated grants

  • Agency: NCI NIH HHS, Id: CA 71818
  • Agency: NIAID NIH HHS, Id: R01 AI026918
  • Agency: NIAID NIH HHS, Id: AI 26918
  • Agency: NIGMS NIH HHS, Id: T32 GM007185
  • Agency: NIDDK NIH HHS, Id: DK 46763
  • Agency: NIAID NIH HHS, Id: R37 AI026918
  • Agency: NIDDK NIH HHS, Id: P01 DK046763

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An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.

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