Mechanisms for recognition of tumor antigens and mediation of anti-tumor effect by noncytolytic Lyt-2+ T cell subset.
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 Ia-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 Ia-positive adherent cells.
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D002738:Chloroquine / Q000494:pharmacology; D005260:Female; D005557:Formaldehyde / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000276:immunology*; D011108:Polymers / Q000494:pharmacology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000950:Antigens, Ly; D000951:Antigens, Neoplasm; D000949:Histocompatibility Antigens Class II; D011108:Polymers; D005557:Formaldehyde; D007371:Interferon-gamma; D002738:Chloroquine; C003043:paraform