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Alteration of interleukin 4 production results in the inhibition of T helper type 2 cell-dominated inflammatory bowel disease in T cell receptor alpha chain-deficient mice.
Iijima H; Takahashi I; Kishi D; Kim JK; Kawano S; Hori M; Kiyono H;
December 30, 1999
J Exp Med. 1999 Sep 6;190(5):607-15. Unique Identifier : AIDSLINE

T cell receptor alpha chain-deficient (TCR-alpha(-/-)) 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-betabeta (CD4(+)betabeta) T cells producing predominantly interleukin (IL)-4. To investigate the role of these Th2-type CD4(+)betabeta T cells, we treated TCR-alpha(-/-) mice with anti-IL-4 monoclonal antibody (mAb). Approximately 60% of TCR-alpha(-/-) 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-alpha(-/-) mice treated with either specific or mock Ab developed CD4(+)betabeta 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 gamma-specific expression. These findings suggest that IL-4-producing Th2-type CD4(+)betabeta T cells play a major immunopathological role in the induction of IBD in TCR-alpha(-/-) mice, a role that anti-IL-4 mAb inhibits by causing Th2-type CD4(+)betabeta T cells to shift to the Th1 type.

JOURNAL ARTICLE Animal Antibodies, Monoclonal/PHARMACOLOGY Cytokines/BIOSYNTHESIS/GENETICS CD4-Positive T-Lymphocytes/IMMUNOLOGY Immunity, Mucosal Immunoglobulins/BIOSYNTHESIS In Vitro Inflammatory Bowel Diseases/ETIOLOGY/*IMMUNOLOGY/*PREVENTION & CONTROL Interferon Type II/BIOSYNTHESIS/GENETICS Interleukin-4/ANTAGONISTS & INHIB/*BIOSYNTHESIS/GENETICS Interleukin-6/BIOSYNTHESIS/GENETICS Intestinal Mucosa/IMMUNOLOGY/PATHOLOGY Mice Mice, Inbred C57BL Mice, Knockout Receptors, Antigen, T-Cell, alpha-beta/*DEFICIENCY/GENETICS RNA, Messenger/GENETICS/METABOLISM Support, Non-U.S. Gov't Th1 Cells/IMMUNOLOGY Th2 Cells/*IMMUNOLOGY