Increased CXCR3 expression associated with CD3-positive lymphocytes in the liver and biliary remnant in biliary atresia.

BACKGROUND

Lymphocyte-mediated inflammatory damage of the bile ducts has been proposed as a potential mechanism in the pathogenesis of biliary atresia (BA). Chemokines regulate leukocyte migration and act as critical organizers of cell distribution in inflammatory responses. The aim of this study was to analyze the infiltration of T lymphocytes and the expression of a chemokine receptor, CXCR3, predominantly expressed on type 1 polarized T cells (T(H)1, T(C)1) in the liver and excised biliary remnants in infants with BA.

METHODS

Immunohistochemistry for CD3, CD8, and CXCR3 was performed using liver biopsy specimens collected from the following 3 age-matched groups of patients: group 1, BA (nonsyndromic) at the time of Kasai portoenterostomy (n = 10); group 2, congenital choledochal dilatation (n = 2); and group 3, other cholestatic diseases including paucity of intrahepatic bile ducts and cholestasis (n = 3) related to total parenteral nutrition. Cellular staining on each section was graded from 0 to 4 and compared using nonparametric statistics.

RESULTS

Infiltrating CD3+ and CD8+ lymphocytes in the portal tracts were significantly increased in group 1 (3.1 +/- 0.4, 2.8 +/- 0.4), compared with groups 2 (1.0 +/- 0.0, 1.0 +/- 0.0) and 3 (1.7 +/- 0.3, 1.5 +/- 0.5) (P < .01, P < .05). CXCR3+ mononuclear cells were significantly increased in group 1 (2.6 +/- 0.3) compared with groups 2 (0.5 +/- 0.5) and 3 (0.7 +/- 0.3) (P < .05). They were mainly found in the portal tracts with a similar distribution to CD3+ cells. CXCR3+ cells and CD3+ cells also showed a similar distribution in specimens of biliary remnants from just below the portal plate.

CONCLUSIONS

Increased expression of CXCR3 associated with a significantly increased CD3 and CD8 T-cell infiltration suggests that CXCR3+ lymphocytes in a type 1 (T(H)1, T(C)1) cytokine milieu may play a role in the pathogenesis of BA.