title: 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.
abstract: 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.
authors.affiliation: Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Iijima
authors.forename: I
authors.initials: I
authors.lastname: Takahashi
authors.forename: D
authors.initials: D
authors.lastname: Kishi
authors.forename: J K
authors.initials: JK
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Kawano
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: H
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D018928:Immunity, Mucosal; D007136:Immunoglobulins / Q000096:biosynthesis; D066298:In Vitro Techniques; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency* / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D007136:Immunoglobulins; D015850:Interleukin-6; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4; D007371:Interferon-gamma