T-cell vaccination in experimental myasthenia gravis: a double-edged sword.
Immunization with antigen-specific T cells has been used successfully in the treatment of several T cell-mediated experimental autoimmune diseases, including experimental allergic encephalomyelitis, thyroiditis, and adjuvant arthritis. The aim of this study was to determine whether T-cell vaccination could be used to down-regulate specifically the antibody response to AChR in experimental autoimmune myasthenia gravis (EAMG), an antibody-mediated disorder. We produced T cells specific for the acetylcholine receptor (AChR) by immunizing Lewis rats with torpedo AChR, harvesting the regional lymph node cells, and restimulating them in vitro with AChR. This cell population was expanded with IL2. The cells were then activated with concanavalin A (Con-A) and exposed to high hydrostatic pressure to augment their immunogenicity. We found that rats vaccinated with these cells did not manifest decreased antibody titers to AChR, when challenged. In fact, the antibody response to AChR was consistently potentiated by the vaccine treatment. This result could not be attributed to antigen carryover by the vaccinating cells or to induction of anti-idiotypic antibodies. Despite these results showing overall enhancement of the AChR antibody response, we found evidence of AChR-specific suppressor cells in the spleens of the vaccinated animals. Our observations indicate that T-cell vaccination can elicit both a positive immune response and a suppressive response in the same animal. If the T-cell vaccination strategy is to be useful for the treatment of MG, methods for amplifying the suppressive effect will need to be developed.
Kahn
C R
CR
Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205.
McIntosh
K R
KR
Drachman
D B
DB
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000917:Antibody Formation; D001323:Autoantibodies / Q000096:biosynthesis; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D006874:Hydrostatic Pressure; D007108:Immune Tolerance; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D009157:Myasthenia Gravis / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011978:Receptors, Nicotinic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014611:Vaccination
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes; D007376:Interleukin-2; D011978:Receptors, Nicotinic; D003208:Concanavalin A