Independent cell types are involved in the induction of antimelanoma responses in C57BL/6 mice immunized with interleukin-2-secreting allogeneic mouse fibroblasts expressing melanoma-associated antigens.
Cellular antimelanoma immune responses developed during the coincubation of spleen cells from naive C57BL/6 mice (H-2b) with LM mouse fibroblasts (H-2k) genetically modified to express melanoma-associated antigens (MAA) and to secrete interleukin (IL)-2 (RLBA-IL-2 cells). Antimelanoma responses also developed following coincubation of spleen cells from naive mice with allogeneic cells (H-2k) that expressed MAA, but did not secrete IL-2 (RLBA-ZipNeo cells), or allogeneic cells (H-2k) that secreted IL-2, but did not form MAA (LM-IL-2 cells). However, in these instances, the magnitude of the responses was significantly less (p < 0.01) than followed coincubation of spleen cells with the allogeneic cell construct (RLBA-IL-2) that combined IL-2 secretion with the expression of MAA. LM(TK-) cells (H-2k) or B16 cells (H-2b) failed to generate antimelanoma immune responses in populations of spleen cells from C57BL/6 mice. The cell types involved in the induction of the antimelanoma response by the genetically modified cells were determined by prior depletion of T-cell subsets with monoclonal antibodies before the addition of the cellular immunogens. Antimelanoma responses failed to develop in spleen cell populations depleted of T-helper cells if the cellular immunogen was non-IL-2 secreting (RLBA-ZipNeo cells). Prior depletion of T-helper cells did not affect the induction of an antimelanoma response in cell populations coincubated with constructs (RLBA-IL-2 or LM-IL-2) modified to secrete IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)
Kim
T S
TS
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago 60680.
Collins
M K
MK
Cohen
E P
EP
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D007114:Immunization; D007376:Interleukin-2 / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology; D008546:Melanoma, Experimental / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000276:immunology*; D014162:Transfection
D000951:Antigens, Neoplasm; D007376:Interleukin-2; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins