Stimulation of tumor-specific cytotoxic T-lymphocyte responses in vitro by hapten-reactive helper T lymphocytes and the allogeneic effect

Abstract

This study was designed to extend recent reports about the ability of hapten-primed T lymphocytes to serve as helper cells, capable of augmenting the generation of tumor-specific CTL in vivo and in vitro, when the priming hapten was coupled to the immunizing tumor cells, and furthermore, to test the influence of the nonspecific immunostimulatory allogeneic effect on such CTL responses. The addition of TNP-MGG-primed spleen cells in culture augmented the in vitro induction of a secondary tumor-specific CTL response upon sensitization of tumor-primed spleen cells against TNP-derivatized tumor cells. These helper cells were found to be radioresistant T cells which could also be triggered to exert their helper function by adding a soluble TNP-MGG conjugate to the cultures, instead of covalently linking the TNP hapten to the tumor cells. The highest levels of tumor-specific CTL activity were achieved when irradiated parental BALB c spleen cells were added to cultures of ( BALB c × A J )F 1 hybrid tumor-primed spleen cells in the presence of TNP-primed helper T cells. These results indicate that specific help provided by hapten-reactive T cells and the nonspecific allogeneic effect may act in concert, leading to highly efficient tumor-specific CTL responses, and suggest new approaches for the potential immunotherapy of growing tumors.