title: Immune activation genes in inflammatory bowel disease.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Cleveland Clinic Foundation, Ohio.
authors.forename: T
authors.initials: T
authors.lastname: Matsuura
authors.forename: G A
authors.initials: GA
authors.lastname: West
authors.forename: K R
authors.initials: KR
authors.lastname: Youngman
authors.forename: J S
authors.initials: JS
authors.lastname: Klein
authors.forename: C
authors.initials: C
authors.lastname: Fiocchi
mesh_terms: 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*
chemical_list: D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2