M. Lampinen*1, A. Fredricsson1, J. Vessby1, A. Wanders2, F. Rorsman1, M. Carlson1
1Uppsala University, Medical Sciences, Uppsala, Sweden, 2Umeå University, Medical Biosciences, Umeå, Sweden
There is a strong association between primary sclerosing cholangitis (PSC) and ulcerative colitis (UC), but the immunological link between the 2 diseases is still unknown. The predominant cell infiltrate in a PSC-affected liver consists of T-lymphocytes. However, the presence and phenotype of colonic T-cells in UC patients with PSC has not previously been investigated. The aim of our study was therefore to compare the colonic T-cell profile in UC patients with and without concomitant PSC. In addition, the activity of colonic neutrophil and eosinophil granulocytes was evaluated.
Included in the study were 13 patients with PSC-UC (5 with active intestinal inflammation), 18 patients with UC (6 active), and 10 controls. Biopsy samples from the right colon, caecum, and rectum were collected. Cell suspensions were prepared and analysed by flow cytometry; cell numbers were confirmed by immunohistochemistry staining. T-cell phenotype was evaluated using a panel of markers for activation and Th1/Th2-polarisation. The presence and activation of neutrophil and eosinophil granulocytes was assessed with specific markers.
Patients with PSC-UC had increased levels of CXCR3-positive CD8+ T-cells but fewer CD25-positive CD4+ T-cells. The finding of downregulated CD4+ CD25-expression in PSC-UC is in line with previous studies on PSC-affected liver.1 UC patients without PSC had an increased CRTH2/CXCR3-quote, indicating a predominance of Th-2 type CD4+ T-cells in this patient group. Eosinophil and neutrophil granulocytes were increased in both patient groups, but significantly less activated in PSC-UC compared with regular UC. Notably, the absence of a Th2-type inflammatory response in PSC-UC may be the reason for the lack of activated eosinophils in PSC-UC.
Our novel data indicate that UC associated with PSC is a distinct disease entity with an aberrant colonic T-cell profile. Importantly, a large fraction of the colonic CD8+ T-cells in PSC-UC express the liver homing receptor CXCR3, thus providing a link between the colonic inflammation and the biliary duct disease in PSC.
 Bo X, Broome U, Remberger M, et al. Tumour necrosis factor alpha impairs function of liver derived T lymphocytes and natural killer cells in patients with primary sclerosing cholangitis. Gut 2001 Jul;49(1):