Mechanisms for Recognition of Tumor Antigens and Mediation of Anti‐tumor Effect by Noncytolytic Lyt‐2+ T Cell Subset

摘要

The mode of anti‐tumor function in vivo of noncytolytic Lyt‐2⁺ T cells from C3H/He mice hyperimmune to syngeneic MH134 hepatoma was investigated in a double diffusion chamber system which was recently established in our laboratory. C3H/He mice were implanted intraperitoneally with the double diffusion chamber unit in which each chamber contained either L3T4⁺ T cell‐depleted MH134‐hyperimmune spleen cells plus mitomycin C‐treated MH134 tumor cells or other syngeneic X5563 viable tumor cells plus normal spleen cells as a source of macrophages. Inclusion of anti‐MH134 Lyt‐2⁺ T cells together with MH134 tumor cells in one chamber resulted in comparable growth inhibition of viable X5563 tumor cells in the other chamber to that obtained by unfractionated MH134‐hyperimmune spleen cells. The induction in the Lyt‐2⁺ T cell‐containing chamber of anti‐tumor effect to be delivered into the other chamber was dependent on the co‐existence of la‐positive adherent cells along with Lyt‐2⁺ T cells. Although adherent cell‐depleted Lyt‐2⁺ T cells regained the inducibility of anti‐tumor immunity when supplemented with splenic adherent cells, the addition of adherent cells pretreated with chloroquine failed to restore the ability of Lyt‐2⁺ T cells to induce their anti‐tumor effect. In addition, paraformaldehyde‐treated MH134 tumor cells instead of untreated tumor cells were not capable of activating Lyt‐2⁺ T cells. These results indicate that a portion of Lyt‐2⁺ T cells exerts their anti‐tumor effect by a mechanism distinct from direct tumor cell lysis and that their activation for mediation of this type of tumor immunity requires the recognition of tumor antigens processed and presented by la‐positive adherent cells.