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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


  • Hagenbaugh A
  • Sharma S
  • Dubinett SM
  • Wei SH
  • Aranda R
  • Cheroutre H
  • Fowell DJ
  • Binder S
  • Tsao B
  • Locksley RM
  • Moore KW
  • Kronenberg M


The Journal of experimental medicine

Publication Data

June 16, 1997

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI 26918
  • Agency: NCI NIH HHS, Id: CA 71818
  • Agency: NIDDK NIH HHS, Id: DK 46763

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