Augmentation of antitumor immune response by trinitrophenyl (TNP)-reactive helper T-cells: enhanced induction of tumor-specific Lyt-1+2- T-cell-mediated delayed-type hypersensitivity from spleen cells of tumor-bearing mice by TNP helpers.

Spleen cells from X5563 tumor-bearing syngeneic C3H/HeN mice were stimulated in vitro with trinitrophenyl (TNP)-modified or unmodified X5563 tumor cells. TNP-reactive helper T-cells obtained from TNP-primed C3H/HeN mice were added to the above cultures in an attempt to augment the induction of anti-X5563 delayed-type hypersensitivity (DTH) responses. The DTH responses were measured by adoptive transfer of cultured cells together with unmodified X5563 cells into footpads of syngeneic mice. Cultures of spleen cells from tumor-bearing mice plus X5563 or TNP-modified X5563 cells failed to generate anti-X5563 DTH responses. In contrast, addition of TNP-helper T-cells to the cultures resulted in appreciable DTH as well as in cytotoxic responses to X5563 tumor cells. Demonstration of this immunity was dependent on the presence of TNP-X5563 tumor cells as stimulators during the culture period. The anti-X5563 DTH effector cells augmented by TNP helpers were found to be of the Lyt-1+2- phenotype and were tumor specific, since DTH responses were observed when the cultured cells were injected with X5563 but not when injected with another syngeneic tumor. These results demonstrate that TNP-helper T-cells are capable of augmenting the induction of tumor-specific Lyt-1+2- T-cell-mediated DTH responses from lymphoid cells of tumor-bearing mice upon the stimulation of TNP-reactive tumor cells. The results are discussed in relation to: a previously described tumor-specific immunotherapy model in which a growing tumor regressed by virtue of TNP helpers and the implications of augmenting induction of tumor-specific DTH responses in antitumor resistance.