Circulating levels of IL-10 are critically related to growth and rejection patterns of murine mastocytoma cells.
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.
Grohmann
U
U
Department of Experimental Medicine, University of Perugia, Italy. pharmpg@tin.it
Silla
S
S
Belladonna
M L
ML
Bianchi
R
R
Orabona
C
C
Puccetti
P
P
Fioretti
M C
MC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002454:Cell Differentiation; D003433:Crosses, Genetic; D005786:Gene Expression Regulation / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology / Q000528:radiation effects; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D015847:Interleukin-4 / Q000032:analysis; D008297:Male; D012515:Mast-Cell Sarcoma / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000637:transplantation; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D011993:Recombinant Fusion Proteins; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma