Mucosal T-cell immunoregulation varies in early and late inflammatory bowel disease.
OBJECTIVE
Crohn's disease is a life-long form of inflammatory bowel disease (IBD) mediated by mucosal immune abnormalities. Understanding of the pathogenesis is limited because it is based on data from adults with chronic Crohn's disease. We investigated mucosal T-cell immunoregulatory events in children with early Crohn's disease.


METHODS
Mucosal biopsies and T-cell clones were derived from children experiencing the first attack of Crohn's disease, children with long-standing Crohn's disease, infectious colitis, and children without gut inflammation.


RESULTS
As in acute infectious colitis, interleukin (IL) 12 induced T cells from early Crohn's disease to acquire a strongly polarised T helper (Th) type 1 response characterised by high IFN-gamma production and IL12Rbeta2 chain expression. Th1 polarisation was not induced in clones from late Crohn's disease. Mucosal levels of IL12p40 and IL12Rbeta2 messenger RNA were significantly higher in children with early than late Crohn's disease. These results demonstrate that susceptibility to IL12-mediated modulation is strongly dependent on the stage of Crohn's disease.


CONCLUSIONS
At the onset of Crohn's disease mucosal T cells appear to mount a typical Th1 response that resembles an acute infectious process, and is lost with progression to late Crohn's disease. 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 which immunomodulation may have optimal therapeutic efficacy.
Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
S
S
Kugathasan
L J
LJ
Saubermann
L
L
Smith
D
D
Kou
J
J
Itoh
D G
DG
Binion
A D
AD
Levine
R S
RS
Blumberg
C
C
Fiocchi
D000293:Adolescent; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003106:Colon / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D053707:Receptors, Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
D016207:Cytokines; C508439:IL12RB2 protein, human; D053762:Interleukin-12 Subunit p40; D012333:RNA, Messenger; D053707:Receptors, Interleukin-12; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma