Interleukin-10 pp 141-148 | Cite as

Interleukin-10 Deficient Mice

  • Donna Rennick
  • Dan Berg
  • Ralf Kühn
  • Werner Müller
Part of the Molecular Biology Intelligence Unit book series (MBIU)


After the mutation which inactivates the IL-4 gene had been introduced into embryonic stem cells, but before the IL-4-deficient mice1 had been generated or analyzed, a new cytokine, designated interleukin-10 (IL-10) was cloned.2 Many of the biological properties of this new cytokine such as the induction of increased expression of MHC class II molecules on B cells3 and a strong inhibitory effect on the production of inflammatory cytokines by macrophages4,5 were similar to those of IL-4. Consequently, it seemed logical to inactivate the IL-10 gene in the mouse germline to elucidate its main biological functions and in the future to combine the two mutations by crossing the mutant mice. As the entire genomic structure of the IL-10 gene was not known at the time of the gene inactivation construct, we decided to replace a portion of its putative first exon by the neomycin gene and to introduce a frame shift mutation into the coding region by destroying an EcoRI site of the genomic clone a site which was later found to be located in the third exon of the gene.6,7


Inflammatory Bowel Disease Ulcerative Colitis Deficient Mouse Pyoderma Gangrenosum Keyhole Limpet Hemocyanin 
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  1. 1.
    Kühn R, Rajewsky K, Müller W. Generation and analysis of interleukin-4 deficient mice. Science 1991; 254: 707–10.PubMedCrossRefGoogle Scholar
  2. 2.
    Moore KW, Vieira P, Fiorentino DR et al. Homology of the cytokine synthesis inhibitory factor (IL-10) to the Epstein Barr virus gene BCRF1. Science 1990; 248: 1230–34.PubMedCrossRefGoogle Scholar
  3. 3.
    Go NF, Castle BE, Barrett R et al. Interleukin-10 (IL-10), a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells. J Ex. Med 1990; 172: 1625–31.CrossRefGoogle Scholar
  4. 4.
    Fiorentino DF, Zlotnik A, Mosmann TR et al. IL-10 inhibits cytokine production by activated macrophages. J Immunol 1991; 147: 3815–22.PubMedGoogle Scholar
  5. 5.
    de Waal-Malefyt R, Haanen J, Spits H et al. IL-10 inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991; 174: 1209–20.PubMedCrossRefGoogle Scholar
  6. 6.
    Kim JM, Brannan CI, Copeland MG et al. Structure of the mouse IL-10 gene and chromosomal localization of the mouse and human genes. J Immunol 1992; 148: 3618–23.PubMedGoogle Scholar
  7. 7.
    Kühn R, Löhler J, Rennick D et al. Interleukin-l0-deficient mice develop chronic enterocolitis. Cell 1993; 75: 263–74.PubMedCrossRefGoogle Scholar
  8. 8.
    Howard M, Farrar J, Hilfiker M et al. Identification of a T cell-derived B cell growth factor distinct from interleukin 2. J Exp Med 1982; 155: 914–23.PubMedCrossRefGoogle Scholar
  9. 9.
    Lee F, Yokota T, Otsuka T et al. Isolation and characteri-zation of a mouse interleukin cDNA clone that expresses B-cell stimulatory factor 1 activities and T-cell-and mastcell-stimulating activities. Proc Natl Acad Sci USA. 1986; 83: 2061–65.PubMedCrossRefGoogle Scholar
  10. 10.
    Paul WE, Ohara J. B cell stimulatory factor- 1/interleukin-4. Annu Rev Immunol 1987; 5: 429–59.PubMedCrossRefGoogle Scholar
  11. 11.
    Ishida H, Hastings R, Kearney J et al. Continuous anti-interleukin-10 antibody administration depletes mice of Ly-1 B cells but not conventional B cells. J Exp Med 1992; 175: 1213–20.PubMedCrossRefGoogle Scholar
  12. 12.
    Bogdan C, Vodovotz Y, Nathan C. Macrophage deactivation by Interleukin-10 J Exp Med 1992; 174: 1549–55.Google Scholar
  13. 13.
    de Waal-Malefyt R, Haanen J, Spits H et al. IL-10 and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II MHC expression. J Exp Med 1991; 174: 915–24.PubMedCrossRefGoogle Scholar
  14. 14.
    Ralph P, Nakoinz I, Sampson Johannes A et al. IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor. J Immunol 1992; 148: 808–14.PubMedGoogle Scholar
  15. 15.
    Hsu D-H, Moore KW, Spits H. Differential effects of interleukins-4 and -10 on interleukin-2-induced interferon-y synthesis and lymphokine-activated killer activity. Int Immunol 1992; 4: 563–69.PubMedCrossRefGoogle Scholar
  16. 16.
    Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse helper T cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Thl clones. J Exp Med 1989; 170: 2081–95.PubMedCrossRefGoogle Scholar
  17. 17.
    Fiorentino DF, Zlotnik A, Vieira P et al. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Thl cells. J Immunol 1991; 146: 3444–51.PubMedGoogle Scholar
  18. 18.
    Taga K, Tosato G. IL-10 inhibits T cell proliferation and IL-2 production. J Immunol 1992; 148: 1143–48.PubMedGoogle Scholar
  19. 19.
    Ding L, Shevach EM. IL-10 inhibits mitogen-induced T cell proliferation by selectively inhibiting macrophage costimulatory function. J Immunol 1992: 148: 3133–39.PubMedGoogle Scholar
  20. 20.
    O’Garra A, Stapleton G, Dhar V et al. Production of cytokines by mouse B cells: B lymphomas and normal B cells produce Interleukin-10. Int Immunol 1990; 2: 821–32.PubMedCrossRefGoogle Scholar
  21. 21.
    O’Garra A, Chang R, Go N et al. Ly-1 B (B-1) cells are the main source of B-cellderived IL-10. Eur J Immunol 1992; 22: 711–17.PubMedCrossRefGoogle Scholar
  22. 22.
    Yssel H, de Waal Malefyt R, Roncarolo MG et al. IL-10 is produced by subsets of human CD4* T cell clones and peripheral blood T cells. J Immunol 1992; 149: 2378–84.PubMedGoogle Scholar
  23. 23.
    Lin TZ, Svetic A, Ganea D et al. Cytokines in NZB CD5* B clones. Ann NY Acad Sci 1992; 651: 581–83.PubMedCrossRefGoogle Scholar
  24. 24.
    Hisatsun T, Minai Y, Nishisima KI et al. A suppressive lymphokine derived from Ts clone 13G2 is IL-10. Lymphokine Cytokine Res 1992; 11: 87–93.Google Scholar
  25. 25.
    Benjamin D, Knobloch TJ, Dayton MA. Human B-cell interleukin-10: B-cell lines derived from patients with acquired immunodeficiency syndrome and Burkitt’s lymphoma constitutively secrete large quantities of interleukin-10. Blood 1992; 80: 1289–98.PubMedGoogle Scholar
  26. 26.
    Rivas JM, Ullrich SE. Systemic suppression of delayed-type hypersensitivity by supernatants from UV-irradiated keratinocytes. An essential role for keratinocyte-derived IL-10. J Immunol 1992; 149: 3865–71.PubMedGoogle Scholar
  27. 27.
    Enk AJ, Katz SI. Identification and induction of keratinocyte-derived IL-10. J Immunol 1992; 149: 92–95.PubMedGoogle Scholar
  28. 28.
    Gocinski BL, Tigelaar RE. Roles of CD4* and CD8* T cells in mucine contact sensitivity revealed by in vivo monoclonal antibody depletion. J Immunol 1990; 144: 4121–28.PubMedGoogle Scholar
  29. 29.
    Piguet PF, Grau GE, Vassalli P. Subcutaneous perfusion of tumor necrosis factor induces local proliferation of fibroblasts, capillaries, and epidermal cells, or massive tissue necrosis. Am J Pathol 1990; 136: 103–09.PubMedGoogle Scholar
  30. 30.
    Piguet PF, Grau, GE, Hauser C et al. Tumor necrosis factor is a critical mediator in hapten-induced irritant and contact hypersensitivity reactions. J Exp Med 1991; 173: 673–79.PubMedCrossRefGoogle Scholar
  31. 31.
    Fong TAT, Mosmann TR. The role of IFNgamma in delayed-type hypersensitivity mediated by Thl clones. J Immunol 1989; 143: 2887–93.PubMedGoogle Scholar
  32. 32.
    Issekutz TB, Stoltz JM, Van der Meide P. Lymphocyte recruitment in delayed-type hypersensitivity. The role of IFN-g. J Immunol 1988; 140: 2989–93.PubMedGoogle Scholar
  33. 33.
    Mosmann TR, Moore, KW. The role of IL-10 in crossregulation of Thl and Th2 responses. Immunol Today 1991; 12: A49–53.PubMedCrossRefGoogle Scholar
  34. 34.
    Sher A, Coffman RL. Regulation of immunity to parasites by T cells and T cell-derived cytokines. Ann Rev Immunol 1992; 10: 385–409.CrossRefGoogle Scholar
  35. 35.
    Urban JF, Madden KB, Svetic A et al. The importance of Th2 cytokines in protective immunity to nematodes Immunol Rev 1992; 127: 205–20.Google Scholar
  36. 36.
    Shanahan F. Pathogenesis of ulcerative colitis. The Lancet 1993; 342: 407–11.CrossRefGoogle Scholar
  37. 37.
    Schreiber S, MacDermott RP, Raedler A et al. Increased activation of isolated intestinal lamina propria mononuclear cells in inflammatory bowel disease. Gastroenterology 1991; 101: 1020–30.PubMedGoogle Scholar
  38. 38.
    Mayer L, Eisenhardt D. Lack of induction of suppresser T cells by intestinal epithelial cells from patients with inflammatory bowel disease. J Clin Invest 1990; 86: 1255–60.PubMedCrossRefGoogle Scholar
  39. 39.
    Mullin GE, Lazenby AJ, Harris ML et al. Increased interleukin-2 messenger RNA in the intestinal mucosal lesions of Crohn’s disease but not ulcerative colitis. Gastroenterology 1992; 102: 1620–27.PubMedGoogle Scholar
  40. 40.
    Kaulfersch W, Fiocchi C, Waldman TA. Polyclonal nature of the intestinal mucosal lymphocyte populations in inflammatory bowel disease. A molecular genetic evaluation of the immunoglobulin and T-cell antigen receptors. Gastroenterology 1988; 95: 364–70.PubMedGoogle Scholar
  41. 41.
    Sadlack B, Merz H, Schorle H et al. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell 1993; 75: 253–61.PubMedCrossRefGoogle Scholar
  42. 42.
    Mombaerts P, Mizoguchi E, Grusby MJ et. al. Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell 1993; 75: 275–82.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • Donna Rennick
  • Dan Berg
  • Ralf Kühn
  • Werner Müller

There are no affiliations available

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