Suppression of tumour-specific cytotoxic T-cell responses against the syngeneic BALB/c plasmacytoma ADJ-PC-5 by tumour-induced CD8+ regulatory T cells via IFN-gamma.
The mechanisms of tolerance induction by tumour cells during early stages of tumourigenesis were analysed in a murine model system using the highly immunogenic BALB/c plasmacytoma ADJ-PC-5. Early stages of tumourigenesis were simulated in syngeneic BALB/c mice by repeated intraperitoneal injections with subimmunogenic doses of X-irradiated ADJ-PC-5 tumour cells. This treatment causes a state of tumour-specific tolerance in a high percentage of mice, involving a population of CD8+ peritoneal T cells which are able to suppress a protective tumour-specific Tc response against this tumour. Using a primary mixed lymphocyte tumour cell culture (MLTC) as an in vitro system to study suppressive mechanisms of such regulatory T cells, the role of production or consumption of a number of cytokines was analysed. The data presented here demonstrate that inhibition of a protective Tc response against ADJ-PC-5 tumour cells is due to IFN-gamma production by suppressive T cells from tolerized mice, but not to IL-2 consumption. In contrast to typical CD8+ Tc cells, ADJ-PC-5-specific CD8+ Tc cells do not produce IFN-gamma and are furthermore suppressed by IFN-gamma. Thus, tumour-induced suppressive T cells and tumour-specific Tc cells seem to represent functionally and phenotypically different subsets of CD8+ T cells, possibly pointing towards a differential activation of type-1 and type-2 CD8+ T cells depending on the dose of tumour cells.
Pauels
H G
HG
Institute for Immunology, University of Münster, Germany.
Specht
C
C
Becker
C
C
Kölsch
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001202:Ascitic Fluid / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016219:Immunotherapy, Adoptive; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D010534:Peritoneal Neoplasms / Q000276:immunology / Q000473:pathology; D010954:Plasmacytoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007371:Interferon-gamma; D007213:Indomethacin