Experimental autoimmune myasthenia gravis (EAMG) has been produced in C57BL/6 mice by immunization with torpedo acetyl choline receptor. Our laboratory has developed suppressor T cell lines and clones derived from lymph node cells of immunized animals. The present proposal concerns three phases. The first two have to do with enriching T cell lines for both helper and suppressor activity and hybridizing these lines to form immortalized T cell hybridomas. Our method will be to induce suppressor T cells by a variety of means including antigen coupled cells, and by pretreating the animals with total lymphoid irradiation. Cells from animals in whom suppressor cells have been induced will be enriched by both panning and rosetting means prior to hybridization. Finally, T cells will be hybridized and selected for the capacity to suppress lymph node cell proliferation of immunized lymph node cells, and to suppress antibody production in vitro and delayed type hypersensitivity as measured both by ear swelling and footpad swelling. The production of helper T cell hybrids will be used to facilitate study of the potential augmentation of the development of experimental autoimmune myasthenia gravis in mouse strains. If transfer of helper hybrids induces the disease in susceptible strains, then means of attenuation of such hybrids with chemical, drug or X-ray are contemplated. A major new thrust of the present proposal is the study of network induced myasthenic syndrome. In this syndrome weakness is induced by immunization of animals with the idiotypic antibodies produced by ligands of the acetylcholine receptor. This syndrome is, in many respects, closer to the model of human disease then is that produced in experimental autoimmune myasthenia after immunizing animals with the torpedo acetyl choline receptor. Two ligands will be used to study this system: siamese cobra neurotoxin, and anti-AChR antibodies. In both the parts of this proposal our use of the network is to understand natural regulatory factors in the immune system leading to the development of clinical myasthenia and thereby hoping to modulate these factors. We have recently been successful in immunizing mice and producing EAMG with a 32 amino-acid oligopeptide of the acetylcholine receptor. This peptide will now be studied as an inducer of suppressor cells, helper cells, and as a toleragen.
| Brooks, E B; Pachner, A R; Drachman, D B et al. (1990) A sensitive rosetting assay for detection of acetylcholine receptor antibodies using BC3H-1 cells: positive results in 'antibody-negative' myasthenia gravis. J Neuroimmunol 28:83-93 |
| Pachner, A R; Kantor, F S; Mulac-Jericevic, B et al. (1989) An immunodominant site of acetylcholine receptor in experimental myasthenia mapped with T lymphocyte clones and synthetic peptides. Immunol Lett 20:199-204 |
| Pachner, A R; Sourojon, M; Fuchs, S (1986) Anti-idiotypic antibodies to anti-acetylcholine receptor antibody: characterization by ELISA and immunoprecipitation assays. J Neuroimmunol 12:205-14 |
