Liver Injury and Invariant NKT Cells Activation by Alpha-galactosylceramide

Abstract

Both free alpha-galactosylceramide (αGalCer) and αGalCer loaded dendritic cells (DCG) activate invariant NaturalKiller T (iNKT) cells. Interestingly, although both free αGalCer and DCG treatment induce liver injury, DCG treatment doesn’t cause lethal liver injury compared with free αGalCer treatment. DCG may be able to activate iNKT cells directly in vivo. On the other hand, free αGalCer are taken by CD1d-positive cells and CD1d-positive cells present CD1d-αGalCer complex for iNKT cells in vivo. Specialized antigen-presenting cells such as dendritic cells may play antigen presentation for iNKT cells, however, how other CD1d positive cells participate in this reaction is not clear. Using CD31 antibody and sorting technique, we separate CD31 negative hepatocyte (HC) and CD31 positive endothelial cells (EC). Both CD31 negative HC and CD31 positive EC are CD1d-positive cells. We showed that CD31 positive EC were more injured after free αGalCer treatment than after DCG treatment. Moreover, EC from mice treated with free αGalCer induced naïve hepatic lymphocyte to produce TNF, which play pivotal role in liver injury by both free αGalCer and DCG treatment, and EC from mice treated with DCG did not. These results indicate that EC play antigen presentation for iNKT cells after free αGalCer treatment and injury of EC may relate to lethal liver injury.