Abstract
Previously tumorigenic P815 tumor cells are rejected by histocompatible mice after transfection with a mutated retroviral gene, and the host is made resistant to subsequent challenge with tumorigenic (control) cells transfected with the nonmutated sequence. To functionally characterize the class I-restricted response to the tumor cell vaccine, we have assessed the in vitro (by CD8+ cells) and in vivo production of type 1 or type 2 cytokines in mice injected with either type of transfected P815 derivative. IL-12 and IL-10 were selectively or preferentially expressed by the regressor mice, and this correlated with the detection of functional type 1 reactivity in vivo (i.e., delayed-type hypersensitivity). Other cytokines were produced by the regressor mice only in vitro (IFN-gamma) or were not detected at all with either type of tumor recipient (IL-4). By means of monoclonal antibody-mediated neutralization or enhancement of endogenous cytokine levels, IL-10 was found to serve an important role in the growth and rejection patterns of the transfected P815 derivatives. In addition to previous evidence for an IL-12 requirement in promoting anti-P815 reactivity, these data establish IL-10 as an important cytokine in permitting optimal expression of this reactivity, which apparently develops in the absence of a strong bias toward a type 1 or type 2 cytokine response.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cancer Vaccines / immunology*
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Cell Differentiation
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Crosses, Genetic
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Gene Expression Regulation / immunology
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Graft Rejection / immunology
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Graft Survival / immunology
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Graft Survival / radiation effects
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Hypersensitivity, Delayed / immunology
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Immunologic Memory
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Interferon-gamma / biosynthesis
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Interferon-gamma / genetics
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Interleukin-10 / antagonists & inhibitors
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Interleukin-10 / biosynthesis
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Interleukin-10 / blood
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Interleukin-10 / genetics
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Interleukin-10 / physiology*
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Interleukin-12 / biosynthesis
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Interleukin-12 / blood
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Interleukin-12 / genetics
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Interleukin-4 / analysis
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Male
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Mast-Cell Sarcoma / immunology*
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Mast-Cell Sarcoma / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred DBA
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Neoplasm Transplantation
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / pharmacology
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Retroviridae Proteins, Oncogenic / genetics
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Retroviridae Proteins, Oncogenic / immunology
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T-Lymphocyte Subsets / immunology*
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Th1 Cells / immunology
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Th1 Cells / metabolism
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Th2 Cells / immunology
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Th2 Cells / metabolism
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Transfection
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Tumor Cells, Cultured / immunology
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Tumor Cells, Cultured / transplantation
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / immunology
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Whole-Body Irradiation
Substances
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Antibodies, Monoclonal
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Antigens, Neoplasm
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Cancer Vaccines
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Recombinant Fusion Proteins
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Retroviridae Proteins, Oncogenic
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Viral Envelope Proteins
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Interleukin-10
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Interleukin-12
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Interleukin-4
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Interferon-gamma