Article Text
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 γ (IFN-γ) 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-γ 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-γ production and with augmentation of surface expressed IL-12 receptor β2.
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.
- CD, Crohn’s disease
- UC, ulcerative colitis
- NL, normal control
- IL, interleukin
- IL-12Rβ2, IL-12 receptor β2
- LPMC, lamina propria mononuclear cell
- PBMC, peripheral blood mononuclear cell
- T-bet, T-box expressed in T cells
- TCR, T cell receptor
- Th1, T helper cell type 1
- IFN-γ, interferon γ
- mAb, monoclonal antibody
- TNF-α, tumour necrosis factor α
- PCR, polymerase chain reaction
- AU, arbitrary units
- TGF-β, transforming growth factor β
- T-bet
- Crohn’s disease
- ulcerative colitis
- interleukin 12
- interleukin 18
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- CD, Crohn’s disease
- UC, ulcerative colitis
- NL, normal control
- IL, interleukin
- IL-12Rβ2, IL-12 receptor β2
- LPMC, lamina propria mononuclear cell
- PBMC, peripheral blood mononuclear cell
- T-bet, T-box expressed in T cells
- TCR, T cell receptor
- Th1, T helper cell type 1
- IFN-γ, interferon γ
- mAb, monoclonal antibody
- TNF-α, tumour necrosis factor α
- PCR, polymerase chain reaction
- AU, arbitrary units
- TGF-β, transforming growth factor β