Effect of helper T cells on prevention of tolerance induction in effector T cells responsible for syngeneic tumor immunity.

The present study investigates the role of helper T cells in preventing tolerance in effector T cells responsible for syngeneic tumor immunity. Tolerance in T cell-mediated immune responses against X5563 plasmacytoma was induced in syngeneic C3H/He mice by intravenous (iv) administration of 7,000 R X-irradiated X5563 tumor cells. Since the anti-X5563 tumor tolerance was observed irrespective of whether the tumor cells had been modified with trinitrophenyl (TNP) hapten prior to iv inoculation, the ability of TNP-reactive helper T cells to prevent the tolerance induced by iv inoculation of TNP-X5563 tumor cells was examined. TNP-reactive helper T cell activity was generated in C3H/He mice by immunization with TNP-isologous mouse gamma-globulin after inoculation with the TNP-conjugate of a non-immunogenic co-polymer of D-glutamic acid and D-lysine. Intravenous inoculation with TNP-modified X5563 cells induced tolerance in mice not primed with TNP. However, such tolerance was prevented in mice in which TNP-reactive helper T cell activity had been generated. These results indicate that helper T cells play a crucial role in preventing effector T cell tolerance. The mechanisms by which tolerance induction in effector T cells is circumvented are discussed in relation to the generation and delivery of signals required for T cell activation.