Immune activation genes in inflammatory bowel disease.
BACKGROUND
Inflammatory bowel disease is associated with enhanced activation of T cells, but the genes responsible for this state are not well characterized.


METHODS
T-cell activation genes were studied in peripheral blood and intestinal mucosal mononuclear cells of control, Crohn's disease, and ulcerative colitis patients.


RESULTS
In all groups the expression of interleukin-2 (IL-2), IL-2 receptor alpha (IL-2R alpha), and IL-2R beta messenger RNA (mRNA) was significantly higher in intestinal than circulating cells, and it correlated well with protein levels. Both IL-2R alpha and IL-2R beta mRNA were abundant in mucosal cells, suggesting that a substantial number of them displays high affinity IL-2R. This would explain why intestinal cells proliferate more, express more IL-2 transcripts, and secrete more IL-2 than peripheral cells. Inflammatory bowel disease cells produced similar or higher IL-2R alpha and IL-2R beta mRNA than controls but generated significantly lower IL-2 mRNA. Thus, the reported defect of IL-2 activity in Crohn's disease and ulcerative colitis is probably related to decreased IL-2 transcription. Crohn's disease intestinal cells had the highest expression of IL-2R gene products. This provides a mechanism for their increased response to IL-2 and supports claims that elevated soluble IL-2R alpha serum levels reflect gut T-cell hyperactivity in this disease.


CONCLUSIONS
These findings underscore the importance of T cells in mucosal immunity and indicate that abnormal T-cell activation is intimately associated to the pathogenesis of inflammatory bowel disease.
Matsuura
T
T
Department of Gastroenterology, Cleveland Clinic Foundation, Ohio.
West
G A
GA
Youngman
K R
KR
Klein
J S
JS
Fiocchi
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003093:Colitis, Ulcerative / Q000276:immunology; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism; D007376:Interleukin-2 / Q000097:blood / Q000235:genetics*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2