Differential cytokine requirements for regulation of autoimmune gastritis and colitis by CD4(+)CD25(+) T cells

J Autoimmun. 2001 Mar;16(2):115-23. doi: 10.1006/jaut.2000.0473.


Murine autoimmune gastritis, induced by neonatal thymectomy or the injection of CD25-depleted lymphocytes into nu/nu recipients, is characterized by an inflammatory infiltrate into the gastric mucosa, parietal cell destruction and circulating anti-parietal cell antibodies. Using RAG-2(-/-)mice as recipients, we determined that the induction of disease relies on CD4(+)CD25(-)effector cells and prevention relies on CD4(+)CD25(+)regulatory cells; neither requires participation of CD8 cells or B cells. The severity of gastritis was dependent on the cytokine repertoire of CD4(+)CD25(-)effector T cells. Recipients of IL-4(-/-)T cells developed more severe gastritis and recipients of INF-gamma(-/-)T cells developed milder disease than recipients of wildtype or IL-10(-/-)effector T cells. Gastritis did not develop in the absence of IL-12. Protection from gastritis does not require either IL-4 or IL-10 because CD4(+)CD25(+)cells from IL-4(-/-)or IL-10(-/-)mice completely abrogated the disease process. CD4(+)CD25(+)cells also protected RAG-2(-/-)recipients from colitis and inhibitory activity was partially dependent on IL-10 expression. These findings highlight the critical role of CD4(+)CD25(+)regulatory T cells in protection from several autoimmune syndromes and delineate the differential contribution of IL-10 to CD4(+)CD25(+)Treg activity in the settings of gastritis and colitis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Colitis / immunology*
  • Colitis / prevention & control
  • DNA-Binding Proteins / genetics
  • Disease Models, Animal
  • Gastritis / immunology*
  • Gastritis / prevention & control
  • Interferon-gamma / immunology*
  • Interleukin-10 / immunology*
  • Interleukin-12 / immunology*
  • Interleukin-4 / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Receptors, Interleukin-2 / immunology*


  • DNA-Binding Proteins
  • Rag2 protein, mouse
  • Receptors, Interleukin-2
  • V(D)J recombination activating protein 2
  • Interleukin-10
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma