Background & Aims: Crohn's disease (CD) is a life-long form of inflammatory bowel disease (IBD) mediated by mucosal immune abnormalities. Understanding of pathogenesis is limited because based on data from adults with chronic CD. We investigated mucosal T-cell immunoregulatory events in children with early CD.
Methods: Mucosal biopsies and T-cell clones were derived from children experiencing the first attack of CD, children with longstanding CD, infectious colitis, and children without gut inflammation.
Results: As in acute infectious colitis, IL-12 induced T-cells from early CD to acquire a strongly polarized Th1 response characterized by high IFN-production and IL-12R2 chain expression. Th1 polarization was not induced in clones from late CD. Mucosal levels of IL-12p40 and IL-12R2 mRNA were significantly higher in children with early than late CD. These results demonstrate that susceptibility to IL-12-mediated modulation is strongly dependent on the stage of CD.
Conclusions: At the onset of CD mucosal T-cells appear to mount a typical Th1 response that resembles an acute infectious process, and is lost with progression to the late CD. This suggests that mucosal T-cell immunoregulation varies with the course of human IBD. Patients with the initial manifestations of IBD may represent an ideal population in where immunomodulation may have optimal therapeutic efficacy.
- Crohn's disease
- ulcerative colitis