Monoclonal antibody against lymphocyte function-associated antigen 1 inhibits the formation of primary biliary cirrhosis-like lesions induced by murine graft-versus-host reaction

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Abstract
Interaction between intercellular adhesion molecule 1 (ICAM‐1) and lymphocyte function‐associated antigen 1 (LFA‐1) might be involved in the pathogenesis of liver diseases. We investigated whether monoclonal antibodies (mAbs) against these two adhesion molecules could inhibit the formation of primary biliary cirrhosis (PBC)‐like lesions in an animal model using graft‐versus‐host reaction (GVHR) with major histocompatibility complex class II disparity. PBC‐like hepatic lesions such as cellular infiltration of portal area and nonsupprative destructive cholangitis (NSDC) were generated by injecting spleen T cells of C57BL/6 (B6) mice into (B6. C‐H‐2bm12 X B6) F1 mice. In the liver of these mice, increased number of LFA‐1‐positive cells and enhanced expression of ICAM‐1 on sinusoidal endothelial cells and bile duct epithelial cells were observed immunohistochemically, when compared with F1 mice without GVHR. Hepatic lesions of these mAb‐treated mice were almost completely inhibited in these mice compared with GVHR mice. Furthermore, we studied to determine which anti‐LFA‐1 mAb or anti‐ICAM‐1 mAb was essential to inhibit the hepatic lesions. Mice solely treated with anti‐LFA‐1 mAb showed significant inhibition of hepatic lesions, whereas treatment with anti‐ICAM‐1 mAb could not inhibit the lesions. Despite the inhibition of hepatic lesions, induction of GVHR and production of antimitochondrial antibodies were not impaired in mAb‐treated mice. We conclude that LFA‐1 mediates cell infiltration into the liver in this murine model of GVHR and suggest a possible therapeutic role of mAbs to this adhesion molecule in selective autoimmune liver diseases.

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