A role for mast cells and the vasoactive amine serotonin in T cell-dependent immunity to tumors.
The involvement of mast cells in anti-tumor resistance was studied by employing 2 strains of mast cell deficient but otherwise immunocompetent mice on a C57BL/6 (H-2b) background (W/Wv and Sl/Sld) and their respective normal +/+ littermate controls. Sensitization of control mice with irradiated semisyngeneic B16 melanoma cells (H-2b) resulted in protection against subsequent challenge with viable B16 cells, in contrast to sensitization of either W/Wv or Sl/Sld mice. The involvement of serotonin in antitumor resistance was studied by employing 2 serotonin active drugs: reserpine, that depletes mast cells of serotonin; and methysergide, a serotonin antagonist. Sensitization of BDF1 mice with irradiated B16 cells and sensitization of DBA/2 mice (H-2d) with irradiated SL2 cells (H-2d) resulted in protection against subsequent challenge with viable B16 cells and viable SL2 cells, respectively. Treatment with either reserpine or methysergide resulted in a decreased protection. Delayed-type hypersensitivity (DTH) footpad responses to allogeneic L5178Y (H-2d) tumor cells in C57BL/6 mice showed a biphasic reaction pattern, similar to that found in DTH responses to simple reactive haptens, such as picryl chloride. Moreover, the early swelling responses were also dependent on T cells and on mast cells. BDF1 mice carrying a semisyngeneic L5178Y tumor on the chest showed an early swelling response after footpad challenge but no late response, possibly indicating that selective down regulation of the late component of DTH was associated with progressive tumor growth in these animals. The biphasic patterns of DTH to both tumor cells and picryl chloride and the T cell and mast cell dependence of both antitumor resistance and DTH to tumor cells suggest that T cell-dependent activation of mast cells to allow entry of mononuclear leukocytes into sites of tumor growth is similar to the mechanism that occurs in DTH.
D000818:Animals; D006183:H-2 Antigens / Q000235:genetics; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D007113:Immunity, Innate; D007116:Immunization, Passive; D007700:Kinetics; D007940:Leukemia L5178 / Q000276:immunology*; D007942:Leukemia, Experimental / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D009368:Neoplasm Transplantation; D012701:Serotonin / Q000502:physiology*; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
D006183:H-2 Antigens; D012701:Serotonin