Autoimmune hepatic inflammation by vaccination of mice with dendritic cells loaded with well-differentiated hepatocellular carcinoma cells and administration of interleukin-12.

Clinical immunology (Orlando, Fla.)

PubMedID: 16246626

Tamaki S, Homma S, Enomoto Y, Komita H, Zeniya M, Ohno T, Toda G. Autoimmune hepatic inflammation by vaccination of mice with dendritic cells loaded with well-differentiated hepatocellular carcinoma cells and administration of interleukin-12. Clin Immunol. 2005;117(3):280-93.
Vaccination of mice with dendritic cells loaded with Hepa1-6, well-differentiated hepatocellular carcinoma cell line (DC/Hepa1-6), induced cytotoxic T lymphocytes against Hepa1-6. Liver-specific inflammation was generated by vaccination of mice with DC/Hepa1-6 and subsequent administration of interleukin (IL)-12. Vaccination with DCs loaded with MC38 or B16 and administration of IL-12 did not generate significant liver-specific inflammation. Splenic T cells from DC/Hepa1-6-vaccinated mice showed proliferative response by stimulation with S-100 protein of the liver and showed cytotoxic activity to hepatocytes. Hepatic mononuclear cells from DC/Hepa1-6 + IL-12-treated mice also showed cytotoxic activity to hepatocytes. Adoptive transfer of splenocytes from DC/Hepa1-6-vaccinated mice produced hepatic inflammation in recipient mice that had been pretreated with IL-12. IL-12 upregulated the expression of adhesion molecules and chemokines in the liver. In conclusion, CTLs responsive to hepatocytes induced by DC/Hepa1-6 and enhanced expression of adhesion molecules and chemokines in the liver by IL-12 would produce autoimmune hepatic inflammation.