RESCUE OF AUTOIMMUNE HEPATITIS BY SOLUBLE MHC-II MOLECULES IN AN IN VITRO AND IN VIVO MURINE EXPERMENTAL MODEL
- KATERINA BAKELA, Greece
Abstract
Background and Aims
Soluble MHC class II (sMHC-II) molecules are present in all body fluids of healthy individuals and have been described as molecules maintaining tolerance through the suppression of autoreactive T lymphocytes. Since sMHC-II were successfully shown to alleviate Systemic Lupus Erythematosus symptoms in an experimental mouse model, in the present study it was attempted to administer sMHC-II to a model of experimental, concanavalin A (conA) induced autoimmune hepatitis (AIH).
Methods
This model highly represents the chronic liver inflammation in AIH and is examined by imbalanced interleukin secretion in serum. Experimental tests were performed both in vitro and in vivo.
Results
Following the mitogenic stimulation of spleen cells with conA in vitro, syngeneic sMHC-II, isolated from healthy mouse serum and identified by ELISA and SDS-PAGE, lead to a significant reduction of activated spleen cells, as assessed by tritiated thymidine incorporation assays. The in vivo experimental model was induced by conA injections in male BALB/c mice. The administration of syngeneic sMHC-II in conA-treated mice showed a significant reduction in the levels of IL-2, IL-4 and IL-10, as well as a decrease in the number of the activated splenic T-lymphocytes, as tested by ELISA and immunofluorescence experiments, respectively. In addition, a slower progression in the phenotypical characteristics of the disease was observed, while liver scans showed milder tissue damage in mice who had received sMHCII.
Conclusions
Therefore, the results presented in this study confirm the suppressive ability of the sMHC-II molecules in the model of experimental AIH, possibly highlighting new therapeutic approaches for autoimmune diseases.