The overall objective of this project is to study the effects of regulatory T lymphocytes on humoral immunity, with a major emphasis on the use of cloned myeloma cells secreting antibodies of defined specificity as targets for such immunoregulation. We have found that suppressor T lymphocytes (Ts) specific for idiotypic determinants of myeloma proteins suppress antibody secretion by the relevant myeloma. Moreover, in a somatic cell hybrid line derived by fusion of two idiotypically unrelated myelomas, Ts specific for each idiotype selectively suppress secretion of only that antibody. Further experiments will be done to optimize experimental conditions by obtaining maximal functional suppression. The effects of Ts on antibody synthesis and post-synthetic glycosylation will be studied by pulsing suppressed myeloma cells with radioactive precursors. The long-term goal is to analyze the effects of Ts on gene transcription and translation by myeloma targets. In another system we have observed that hapten-specific cytolytic T lymphocytes (CTL) inhibit the function of syngeneic hapten-binding myelomas in the presence of hapten-proteins. The target determinants recognized by such CTL will be analyzed, and attempts will be made to generate hapten-specific Ts in order to study their effects on myeloma cells. Finally, the regulation of physiologic antibody responses by anti-hapten CTL and Ts will be studied.
