Suppression of hepatic lesions in a murine graft-versus-host reaction by antibodies against adhesion molecules
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Published on: August 12, 2017
S Itoh1, Y Matsuzaki, T Kimura
1Division of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Background/Aims:
The injection of parental CD4+ T cells into major histocompatibility complex (MHC) class II disparate F1 hybrid mice induced an autoimmune graft-versus-host reaction (GVHR) which is analogous to autoimmune liver diseases. The interaction of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and very late antigen-4 (VLA-4) has been known to be profoundly involved in the trafficking of lymphocytes into the inflammatory tissues. The aim of this study was to clarify the role of VLA4 or VCAM-1 in the development of GVHR-induced hepatic lesions in our model.
Methods:
B6 T spleen cells were injected into (B6.C-H-2bm12xB6) F1 mice intravenously. Anti-VLA-4 mAbs and/or anti-VCAM-1 mAbs were injected intraperitoneally at a dose of 2.5 mg/kg of each mAbs per body weight of mouse. We examined the changes in GVHR-induced hepatic lesions, serum levels of antimitochondrial antibodies (AMA) and cytokine mRNA expressions of liver-infiltrating lymphocytes using H.E. and immunohistochemical staining, enzyme-linked immunosorbent assay (ELISA), and reverse transcription-polymerase chain reaction (RT-PCR), respectively.
Results:
Hepatic lesions of anti-VLA-4 mAbs-treated mice were inhibited compared with those of GVHR mice. However, the administration of mAbs did not interfere with the induction of splenomegaly, the invasion of CD4+, CD8+, B220+, or Mac-1+ cells around bile ducts, nor the production of AMA. Liver-infiltrating CD4+ T cells obtained from these treated mice did not alter the expression of T helper (Th)1 and Th2 cytokine mRNA.
Conclusion:
The results suggest that treatment with antibodies against these adhesion molecules could inhibit the infiltration of lymphocytes without affecting the Th1/Th2 balance. The blockade of VLA-4-mediated cell infiltration into the liver in this model may have a possible novel therapeutic role of VLA-4 mAbs.
