T Cells of Mice Treated with mPEG-Myasthenogenic Peptide Conjugate are Involved in Protection against EAMG by Stimulating Lower Pathogenic Antibody Responses

Abstract

Experimental autoimmune myasthenia gravis (EAMG) can be induced in C57BL/6 (B6) mice by immunization with Torpedo califomka acetylcholine receptor (fAChR). We had previously shown that pretreatment with a monomethoxypolyethylene glycol (mPEG) conjugate of myasthenogenic fAChR α-chain peptide α125-148 (mPEG-peptide) suppressed EAMG. In order to understand the mechanism involving T cells in the induction of this suppression, we have studied, in the present work, the in vitro responses of T cells from mPEG-peptide treated B6 mice after an initial fAChR injection to determine the early effect of mPEG-peptide treatment on these responses. Treatment with mPEG-peptide reduced the T cell responses to fAChR and several fAChR α-chain peptides. To further investigate the T cell helper function in vivo, we transferred T cells from B6 mice that received either mPEG-peptide or control PBS followed by two fAChR injections to non-immune B6 mice. T cell transfer from mPEG-peptide pretreated mice down regulated, in recipient mice, Ab induction (after cell transfer) and Ab production (after two fAChR injections) toward a-chain peptides. Treatment of B6 mice with mPEG-peptide did not alter the ability of their APC to present peptide al46-162 to peptide-specific B6 T cells. The results indicate that suppression of EAMG by treatment with mPEG- peptide is due to T cell involvement and not to a defect in APC function.

Key Words:

• Acetylcholine receptor
• Tolerogen-peptide conjugate. Myasthenia gravis
• T cells
• Antibodies