The mechanism of tolerance induction of tumor-specific delayed-type hypersensitivity responses by intravenous inoculation of tumor cells.
C3H/HeN mice were inoculated intravenously (iv) with 10(6) 10000-R X-irradiated syngeneic MCH-1-A1 fibrosarcoma cells 3 times at 4-day intervals (pretreatment). Spleen cells from these pretreated or normal mice were sensitized in vitro to MCH-1-A1 tumor cells and effector cells generated after 5 days of culture were assayed for delayed-type hypersensitivity (DTH) responses by an adoptive transfer into footpads of syngeneic recipient mice together with MCH-1-A1 cells. Normal spleen cells stimulated with MCH-1-A1 tumor cells generated appreciable anti-MCH-1-A1 DTH responses, whereas spleen cells from the above pretreated mice failed to induce anti-MCH-1-A1 DTH responses. These pretreated spleen cells did not inhibit the generation of DTH responses when co-cultured with normal spleen cells as responding cells. Since vaccinia virus-reactive helper T cells are capable of enhancing DTH responses against antigens co-expressed on vaccinia-infected cells, their ability to augment anti-MCH-1-A1 DTH responses from the pretreated spleen cells upon stimulation with vaccinia-infected MCH-1-A1 cells was investigated. The results demonstrate that under conditions in which enhanced anti-MCH-1-A1 DTH responses were obtained by supplementing vaccinia helper T cells, these vaccinia-helpers were not able to generate any significant DTH responses from the pretreated spleen cells. These results indicate that iv inoculation of tumor cells suppresses the generation of tumor-specific DTH responses not by inducing suppressor cell activity, but rather by inhibiting DTH effector clones themselves.
D000818:Animals; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology