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Original Article

Alteration of Interleukin 4 Production Results in the Inhibition of T Helper Type 2 Cell–Dominated Inflammatory Bowel Disease in T Cell Receptor Chain–Deficient Mice

^a From the Department of Mucosal Immunology, Research Institute for Microbial Diseases, the
^b Department of Internal Medicine and Therapeutics, Osaka University, Osaka 565-0871, Japan
^c First Department of Surgery, Osaka University, Osaka 565-0871, Japan
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.81-6-6878-676581-6-6879-8294

kiyono{at}biken.osaka-u.ac.jp

T cell receptor chain–deficient (TCR-^–/–) mice are known to spontaneously develop inflammatory bowel disease (IBD). The colitis that develops in these mice is associated with increased numbers of T helper cell (Th)2-type CD4⁺TCR-ββ (CD4⁺ββ) T cells producing predominantly interleukin (IL)-4. To investigate the role of these Th2-type CD4⁺ββ T cells, we treated TCR-^–/– mice with anti–IL-4 monoclonal antibody (mAb). Approximately 60% of TCR-^–/– mice, including those treated with mock Ab and those left untreated, spontaneously developed IBD. However, anti–IL-4 mAb–treated mice exhibited no clinical or histological signs of IBD, and their levels of mucosal and systemic Ab responses were lower than those of mock Ab–treated mice. Although TCR-^–/– mice treated with either specific or mock Ab developed CD4⁺ββ T cells, only those treated with anti–IL-4 mAb showed a decrease in Th2-type cytokine production at the level of mRNA and protein and an increase in interferon –specific expression. These findings suggest that IL-4–producing Th2-type CD4⁺ββ T cells play a major immunopathological role in the induction of IBD in TCR-^–/– mice, a role that anti–IL-4 mAb inhibits by causing Th2-type CD4⁺ββ T cells to shift to the Th1 type.

Key Words: inflammatory bowel disease • T cell receptor chain–deficient mice • interleukin 4 • mucosal immunity • pathogenic T cell • Th2-induced colitis

1used in this paper: CD4+βdim, CD4+TCR-–/β+; CD4+ββ, CD4+TCR-ββ; ELISPOT, enzyme-linked immunospot; IBD, inflammatory bowel disease; LP, lamina propria; MLN, mesenteric lymph node; RT, reverse-transcription; SP, spleen

© 1999 The Rockefeller University Press

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