Selective in vitro inhibition of an antibody response to purified acetylcholine receptor by using antigen-ricin A chain immunotoxin

Abstract

Purified acetylcholine receptor (AChR) covalently coupled to the catalytically toxic A chain of ricin has been used to selectively eliminate rat lymph node cells involved in in vitro anti-AChR antibody responses. The resulting inhibition was specific in view of the lack of such inhibition of anti-Keyhole limpet hemocyanin antibody responses. Furthermore, when fractionated B cell or T cell populations were treated with AChR-A chain, both populations were found to be sensitive to the specific cytotoxicity. However, T cell cytotoxicity required higher concentrations of the immunotoxin. Furthermore, when AChR-immune lymphocytes were treated with AChR-A chain in vitro, they became unable to mediate secondary adoptive transfer responses in vivo. The abrogation of the anti-AChR adoptive response correlated with the lack of muscle weakness characteristic of experimental autoimmune myasthenia gravis. Thus, it is possible, in principle, to eliminate clones of antigen-reactive lymphocytes with antigen-ricin A chain immunotoxins. This lets open the possibility of using such agents in immunotherapeutic approaches to autoimmune disease.