Abstract:
BACKGROUND AND AIMS:Many lines of evidence suggest that T helper cell type 1 (Th1) immune responses predominate in Crohn's disease (CD). Recently, a novel transcription factor T-box expressed in T cells (T-bet) has been reported as the master regulator of Th1 development. This study was designed to investigate the role of T-bet and proinflammatory cytokines in Th1 mediated immunopathology in CD. MATERIALS:CD4+ lamina propria mononuclear cells (LPMCs) were isolated from surgically resected specimens (CD, n = 10; ulcerative colitis (UC), n = 10; normal controls (NL), n = 5). METHODS:(1) T-bet expression of CD4+ LPMCs was examined by quantitative real time polymerase chain reaction and western blotting. (2) T-bet expression of LPMCs stimulated by interleukin (IL)-12/IL-18 was analysed by western blotting. (3) Interferon gamma (IFN-gamma) production and T-bet expression of CD4+ peripheral blood mononuclear cells (PBMCs) were examined with or without stimulation by anti-CD3/CD28 monoclonal antibodies and/or IL-12. RESULTS:(1) T-bet expression of CD4+ LPMCs was increased in CD compared with UC and NL. (2) Synergistically, augmentation of IFN-gamma production by IL-12/IL-18 was independent of T-bet expression in LPMCs. (3) T-bet was induced by T cell receptor stimulation in CD4+ PBMCs. T-bet induction correlated with IFN-gamma production and with augmentation of surface expressed IL-12 receptor beta2. CONCLUSIONS:T-bet induction by antigenic stimulation and subsequent stimulation by macrophage derived IL-12/IL-18 are important for establishing Th1 mediated immunopathology in CD.
journal_name
Gutjournal_title
Gutauthors
Matsuoka K,Inoue N,Sato T,Okamoto S,Hisamatsu T,Kishi Y,Sakuraba A,Hitotsumatsu O,Ogata H,Koganei K,Fukushima T,Kanai T,Watanabe M,Ishii H,Hibi Tdoi
10.1136/gut.2003.024190keywords:
subject
Has Abstractpub_date
2004-09-01 00:00:00pages
1303-8issue
9eissn
0017-5749issn
1468-3288pii
53/9/1303journal_volume
53pub_type
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