Regional Specialisation of T Cell Subsets and Apoptosis in the Human Gut Mucosa: Differences Between Ileum and Colon in Healthy Intestine and Inflammatory Bowel Diseases.
BACKGROUND AND AIMS There is very limited information regarding region specific immunological response in human intestine. We aimed to determine differences in immune compartmentalisation between ileum and colon in healthy and inflamed mucosa. METHODS T cell profile and its apoptosis were measured by flow cytometry, Th1, Th17, Treg [CD4()CD25()FOXP3( double positive [DP, CD3()CD4()CD8( and double negative T cells [DN, CD3()CD4( )CD8( immunohistochemistry [FOXP3, caspase 3] and real time polymerase chain reaction [PCR] [IFN g, IL 17 A, and FOXP3] on biopsies from different regions of healthy intestine and of intestine in inflammatory bowel diseases. RESULTS Healthy colon showed higher percentages of Treg, Th17, and DN, and lower numbers of DP T cells compared with ileum [p 0.05] Some but not all region specific differences were lost in inflammatory conditions. Disease specific patterns were found: a Th1/Th17 pattern and a Th17 pattern in Crohn's disease and ulcerative colitis respectively, whereas a reduction in Th1/Th17 was found in microscopic colitis. In colonic Crohn's disease and microscopic colitis, DN T cells had a pattern inverse to that of Th1/Th17 (increase in microscopic colitis [p 0.05] and decrease in Crohn's disease [p 0.005] Higher levels of lymphocyte apoptosis were found in healthy colon compared with the ileal counterparts [p 0.001] All forms of colonic inflammation presented a dramatic decrease in apoptosis compared with healthy colon. By contrast ileal Crohn's disease showed higher levels of cleaved Caspase( CD3( cells. CONCLUSIONS Immunological differences exist in healthy gastrointestinal tract. Inflammatory processes overwhelm some location specific differences, whereas others are maintained. Care has to be taken when analysing immune response in intestinal inflammation, as location specific differences may be relevant.
Journal of Crohn's colitis