Soluble MHC MHC class II II ‐driven therapy for a systemic lupus erythematosus murine experimental in?vitro and in?vivo model

摘要

Abstract Taking into consideration the multiparametric nature of systemic lupus erythematosus ( SLE ), the severity and variability of symptoms and the lack of effective therapeutic approaches, this study took advantage of the recently described role of soluble major histocompatibility complex class II ( sMHCII ) molecules in maintaining tolerance to the organism and attempted to apply sMHCII proteins as a treatment to murine SLE experimental models in?vitro as well as in?vivo. After breaking tolerance to DNA in?vitro, which was accompanied by development of specific anti‐ds DNA antibodies, syngeneic or allogeneic sMHCII molecules, purified from healthy mouse serum, could significantly reduce the specific antibody levels and drive the system towards immunosuppression, as assessed by specific marker analysis on T cells and cytokine production by flow cytometry and ELISA , respectively. The in?vivo experimental model consisted of pristane‐induced SLE symptoms to BALB /c mice, which developed maximal levels of anti‐ds DNA 2?months after pristane inoculation. Syngeneic or allogeneic sMHCII administration could alleviate pristane‐induced symptoms, significantly decrease specific anti‐ds DNA antibody production and develop immunosuppression to the host, as manifested by increase of CD 4?+? CTLA ‐4?+? and CD 4?+? CD 25?+? cell populations in the spleen. Thus, the results presented in this study introduced the ability of sMHCII proteins to suppress specific autoantigen response, opening new areas of research and offering novel therapeutic approaches to SLE with expanding features to other autoimmune diseases.