Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells

Immunity. 1994 Oct;1(7):553-62. doi: 10.1016/1074-7613(94)90045-0.


We have described a murine model of IBD that was induced in C.B-17 scid mice by transfer of the CD45RBhi subpopulation of CD4+ T cells from normal BALB/c mice and could be prevented by cotransfer of the CD45RBlo CD4+ T cell subset. Here we have dissected the mechanism of pathogenesis of IBD in this model and used this information for rational immunotherapy of the disease. CD4+ cells from diseased mice displayed a highly polarized Th1 pattern of cytokine synthesis upon polyclonal stimulation in vitro. The administration of anti-IFN gamma MAb to mice soon after T cell transfer prevented development of colitis for up to 12 weeks. Continual neutralization of TNF with anti-TNF MAbs reduced the incidence of severe disease; however, neutralization of TNF during only the first 3-4 weeks had no effect. Severe colitis was completely abrogated in mice treated systemically with rIL-10, but not with rIL-4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Colitis / pathology
  • Colitis / prevention & control
  • Colon / metabolism
  • Inflammatory Bowel Diseases / etiology
  • Inflammatory Bowel Diseases / prevention & control*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukins / biosynthesis
  • Interleukins / pharmacology
  • Leukocyte Common Antigens / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Models, Immunological
  • RNA, Messenger / analysis
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / metabolism
  • Th1 Cells / metabolism*
  • Time Factors
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology


  • Antibodies, Monoclonal
  • Interleukins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Leukocyte Common Antigens