The augmentation of in vitro and in vivo tumor-specific T cell-mediated immunity by amplifier T lymphocytes.

The present study investigates the role of helper (amplifier) T cells in causing enhanced induction of syngeneic tumor immunity. 2,4,6-Trinitrophenyl- (TNP) reactive helper (amplifier) T cell activity was generated in BALB/c mice by immunization with TNP-isologous mouse γ-globulin after inoculation with TNP conjugates of the nonimmunogenic co-polymer of D-glutamic acid and D-lysine (D-GL). Immunization of these mice with TNP-conjugated syngeneic LSTRA tumor cells led to augmented generation of tumor-specific in vitro cytotoxic T cell activity against LSTRA when compared with the degree of cytotoxicity generated in control mice not primed with TNP. In vivo tumor-neutralizing activity was also augmented in the mice in which TNP-reactive amplifier T cells had been generated before immunization with TNP-LSTRA. Spleen cells from these mice exhibited complete tumor neutralization in a Winn assay. In contrast, spleen cells from mice not primed with TNP before immunization with TNP-LSTRA failed to neutralize viable LSTRA tumor cells, exhibiting only a delay in the appearance of the tumor. The magnitude of tumor-neutralizing activity developed in the presence of TNP-amplifier system was as much as 20-fold greater than for control, and this augmented tumor-neutralizing activity was also tumor specific and T cell mediated. Thus, the present system provides an effective manipulation for eliciting enhanced in vivo tumor rejection as well as in vitro cytotoxic response, and illustrates a role of amplifier T cells in augmentation of syngeneic tumor immunity.