Genetic control of hapten-reactive helper T-cell responses and its implications for the generation of augmented antitumor cytotoxic responses.

The genetic control of hapten-reactive helper T-cell activity involved in cytotoxic T-lymphocyte (CTL) responses and its implications for augmenting tumor-specific immunity were studied. C57BL/6N mice were immunized to trinitrophenyl (TNP) or N-iodoacetyl-N'-(5-sulfonic l-naphthyl)ethylenediamine (AED) hapten by inoculation of hapten-modified syngeneic spleen cells. Spleen cells from these hapten-immunized mice were tested for hapten-reactive helper T-cell activity for generation of CTL. TNP-primed spleen cells resulted in only marginal help for the generation of anti-TNP-modified syngeneic spleen cell (TNP-self) CTL response when cocultured with normal C57BL/6N spleen cells (responding cells) in the presence of TNP-self. In contrast, AED-primed spleen cells exhibited appreciable help for AED-induced CTL responses. Furthermore, AED-helper, but not TNP-helper, T-cell activity was demonstrated to augment the generation of antitumor (RBL-5 leukemia) CTL responses from normal syngeneic spleen cells when stimulated with the corresponding hapten-self plus RBL-5 tumor cells. These results indicate that the successful augmentation of syngeneic tumor immunity through T-T-cell interaction with the use of hapten-reactive helper T-cells can depend on selection of the appropriate haptenic reagent in an individual expressing a given major histocompatibility haplotype.