T helper type-2 cells induce ileal villus atrophy, goblet cell metaplasia, and wasting disease in T cell-deficient mice

Gastroenterology. 2003 Mar;124(3):672-82. doi: 10.1053/gast.2003.50092.


Background & aims: T helper (Th) 1 and Th2 cell subsets significantly influence the pathological features of inflammation in the gastrointestinal tract in a distinct manner. It is now established that the transfer of CD4(+)CD45RB(Hi) (RB(Hi)) T cells to either severe combined immunodeficient (SCID) or recombinase activation gene 2-deficient (RAG(-/-)) mice results in a severe granulomatous hypertrophic colitis mediated by Th1 cells. We have modified this approach to address the role of Th2 cells.

Methods: RB(Hi) T cells from wild-type (Wt) mice or mice genetically predisposed to Th2 responses (interferon-gamma-defective [IFN-gamma(-/-)]) with or without B cells were transferred to T cell receptor (TCR)-beta and delta-chain-defective (TCR(-/-)) or SCID mice.

Results: Transfer of Wt RB(Hi) T cells induced wasting disease with severe colitis in the TCR(-/-) mice. In contrast, IFN-gamma(-/-) RB(Hi) T cells induced severe weight loss and hypoalbuminemia without significant inflammation in the colon. The small intestine of these mice exhibited villus atrophy, a decrease in brush-border enzymes, reduced enterocyte proliferation, and an increased number of goblet cells. The presence of B cells was necessary for these changes, because SCID recipients required cotransfer of B cells, together with IFN-gamma(-/-) RB(Hi) T cells for ileal lesions to develop. Treatment of TCR(-/-) recipients of IFN-gamma(-/-) RB(Hi) T cells with anti-IL-4 mAb abrogated both the wasting disease and the villus atrophy.

Conclusions: Dysregulated Th2 cells cause atrophic changes and goblet cell transformation in the small intestinal epithelium and wasting disease mediated by excess interleukin-4 and B cells.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Atrophy
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / transplantation
  • Goblet Cells / pathology*
  • Ileum / pathology*
  • Interferon-gamma / genetics
  • Interleukin-4 / immunology
  • Leukocyte Common Antigens / analysis
  • Lymphocyte Count
  • Metaplasia
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout / genetics
  • Mice, SCID
  • Microvilli / pathology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • T-Lymphocytes / pathology*
  • Th2 Cells / physiology*
  • Wasting Syndrome / etiology
  • Wasting Syndrome / pathology*
  • Wasting Syndrome / physiopathology*
  • Wasting Syndrome / prevention & control


  • Antibodies, Monoclonal
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Interleukin-4
  • Interferon-gamma
  • Leukocyte Common Antigens