It was evaluated in vitro whether it is possible to induce immunogenicity by haptenization of a nonlymphoid rat tumor, BSp6AS, which is known to be antigenic, but nonimmunogenic, in the syngeneic host. The effectivity of "induced immunogenicity' was tested in vivo.
BSp6AS, an NK-and macrophage-resistant variant of a spontaneously arising fibrosarcoma in the BDX rat strain, does not induce a primary or a secondary T cell response after in vivo or in vitro priming. This deficiency in cytotoxic response is due solely to failure of
activation of helper T cells (TI4), since (a) cytotoxic T cells (CTL) can be detected after in vitro stimulation in the presence of interleukin 2 (IL-2)containing medium; and (b) there are no indications for down-regulation of a potential specific immune response by suppressor T cells (Ts). The lack of activation of tumor-specific TH can be bypassed by activation of hapten-specific TI4. Upon coculture with haptenized tumor cells as a stimulator population, both hapten-specific and tumor-specific CTL are activated by hapten-specific T H.
In line with the findings in vitro, no transplant rejection of naive tumor cells was seen after a variety of immunization schedules. But immunized F t hybrids did reject tumor grafts, supporting the hypothesis of lacking help in the syngeneic situation. This could be confirmed in the syngeneic system by adoptive transfer experiments. Tumor-specific CTL, educated in vitro in the presence of lL-2, were ineffective. But complete protection against haptenized, and partial protection against native tumor cells was achieved in the additional presence of hapten-specific T H.
To our knowledge these experiments prove for the first time that hapten-specific TH are efficient in inducing an immune response even against a nonlymphoid, nonimmunogenic tumor, i. e., it is possible (a) to activate tumor-specific CTL and (b) to initiate tumor graft rejection via hapten-specific T.