T cells of mice treated with mPEG-myasthenogenic peptide conjugate are involved in protection against EAMG by stimulating lower pathogenic antibody responses.
Experimental autoimmune myasthenia gravis (EAMG) can be induced in C57BL/6 (B6) mice by immunization with Torpedo californica acetylcholine receptor (tAChR). We had previously shown that pretreatment with a monomethoxypolyethylene glycol (mPEG) conjugate of myasthenogenic tAChR alpha-chain peptide alpha125-148 (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 tAChR injection to determine the early effect of mPEG-peptide treatment on these responses. Treatment with mPEG-peptide reduced the T cell responses to tAChR and several tAChR alpha-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 tAChR 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 tAChR injections) toward alpha-chain peptides. Treatment of B6 mice with mPEG-peptide did not alter the ability of their APC to present peptide alpha146-162 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.
Oshima
M
M
Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030, USA.
Atassi
M Z
MZ
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis*; D005260:Female; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology*; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation
D001323:Autoantibodies; D010455:Peptides; D011950:Receptors, Cholinergic; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol