INDUCTION OF SYNGENEIC CYTOTOXIC LYMPHOCYTES-T AGAINST A B-CELL TUMOR .1. ROLE OF IDIOTYPIC IMMUNOGLOBULIN

In previous studies we showed that idiotypic determinants of a B cell hybrid, 2C3, was involved in the generation of idiotype (Id)-specific noncytolytic CD4+ effector T cells that suppressed the Ig expression of wild type 2C3 tumor. In the present investigation we report that Id+ Ig associated with 2C3 was also capable of eliciting syngeneic cytotoxic T lymphocytes (CTL) when mice were hyperimmunized with irradiated 2C3 cells. These effector cells were predominantly Thy 1.2+, CD8+, and CD4- and highly cytotoxic to 2C3 as shown by in vitro and in vivo assays. The unique idiotypic determinants (private Id) of 2C3 Ig was important in the induction of CTL since these effector cells were generated in mice only after immunization with Id+ 2C3 cells. In contrast, immunization of mice with 6B2, an Ig-loss variant of 2C3, and 1BF7, an unrelated syngeneic B cell hybrid which expresses Ig of the same isotype as that of 2C3 but of different Id, failed to elicit any cytotoxic response. Furthermore, incorporation of anti-idiotypic monoclonal and polyclonal antibodies into culture medium abrogated the activation of CTL during in vitro stimulation of the primed splenocytes. Induction of CTL was also inhibited by anti-MHC class I and anti-CD3 monoclonal antibodies, indicating that CD3-TcR complex of the effector T cells were involved in the recognition of Id+ Ig in the context of MHC class I antigens. These results, together with our previous observation, suggest that the anti-2C3 immune response is mediated by two kinds of effector cells, namely, CD4+ noncytolytic and CD8+ cytotoxic T cells. Moreover, the unique private Id associated with 2C3 plays a pivotal role in the induction of both of these effector cells. © 1992.