Monomethoxypolyethylene Glycol-Modified Cardiac Myosin Treatment Blocks the Active and Passive Induction of Experimental Autoimmune Myocarditis

BACKGROUND: Injecting various protein antigens conjugated to monomethoxypolyethylene glycol (mPEG) results in antigen-specific tolerance to subsequent immunization. In the present study the ability of mPEG-modified cardiac myosin (CM) to block the development of experimental autoimmune myocarditis (EAM) induced by CM immunization or by the transfer of lymphocytes from CM-immunized donors was studied. METHODS AND RESULTS: A/J mice were injected with mPEG-CM before active or passive EAM induction. We examined the suppressive mechanism by the transfer of lymphocytes from mPEG-CM-treated mice into naïve mice. To ascertain the cells responsible for suppressing EAM induction, in vivo or in vitro depletion of CD4(+) or CD8(+) T cells was performed. mPEG-CM administered before active or passive EAM induction markedly suppressed the incidence and severity of EAM and reduced CM-specific antibody responses. When lymphocytes from mPEG-CM treated mice were transferred into naïve mice that were then immunized with CM, the suppressive effect was recapitulated. CONCLUSIONS: mPEG-CM treatment blocked the active and passive induction of EAM.