The mode of recognition of tumor antigens by noncytolytic-type antitumor T cells: Role of antigen-presenting cells and their surface class I and class II H-2 molecules

The present study investigated the role of antigen-presenting cells (APC) in the activation of noncytolytic T cells against tumor antigens. The noncytolytic-type T cells exerted their antitumor effect by producing γ-interferon (IFN-γ) and by activating macrophages as the ultimate effectors. The production of IFN-γ by these noncytolytic T cells following the stimulation with tumor cells required the participation of Ia⁺ APC, since the depletion of APC from cultures of tumor-immunized spleen cells resulted in almost complete inhibition of the IFN-γ production. Both L3T4⁺ and Lyt-2⁺ subsets of T cells were capable of producing IFN-γ, and the requirement of APC for the production of IFN-γ was the case irrespective of whether noncytolytic T cells were of L3T4⁺ or Lyt-2⁺ phenotype. More importantly, it was demonstrated that the production of IFN-γ by L3T4⁺ and Lyt-2⁺ T cells was inhibited by addition of the respective anti-class II and anti-class I H-2 antibody to cultures. These results indicate that antitumor L3T4⁺ or Lyt-2⁺ noncytolytic T cells are activated for the IFN-γ production by recognizing tumor antigens in the context of self-class II or -class I H-2 molecules on APC.