title: T helper type-2 cells induce ileal villus atrophy, goblet cell metaplasia, and wasting disease in T cell-deficient mice.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Gastroenterology, Research Institute, International Medical Center of Japan, Tokyo, Japan. dohi@ri.imcj.go.jp
authors.forename: Taeko
authors.initials: T
authors.lastname: Dohi
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Fujihashi
authors.forename: Toshiya
authors.initials: T
authors.lastname: Koga
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shirai
authors.forename: Yuki I
authors.initials: YI
authors.lastname: Kawamura
authors.forename: Chieko
authors.initials: C
authors.lastname: Ejima
authors.forename: Rie
authors.initials: R
authors.lastname: Kato
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Saitoh
authors.forename: Jerry R
authors.initials: JR
authors.lastname: McGhee
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001284:Atrophy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D020397:Goblet Cells / Q000473:pathology*; D007082:Ileum / Q000473:pathology*; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000032:analysis; D018655:Lymphocyte Count; D008679:Metaplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D016513:Mice, SCID; D008871:Microvilli / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D013601:T-Lymphocytes / Q000473:pathology*; D018418:Th2 Cells / Q000502:physiology*; D019282:Wasting Syndrome / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology* / Q000517:prevention & control
chemical_list: D000911:Antibodies, Monoclonal; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015847:Interleukin-4; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens