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- Title
Suppression of Tumour-Specific Cytotoxic T-Cell Responses Against the Syngeneic BALB/c Plasmacytoma ADJ-PC-5 by Tumour-Induced CD8<sup>+</sup> Regulatory T Cells Via IFN-γ.
- Authors
Pauels, H.-G.; Specht, C.; Becker, C.; Kölsch, E.
- Abstract
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-γ production by suppressive T cells from tolerized mice, but not to IL-2 consumption. In contrast to typical CD8+ Tc cells, ADJ-PC-5-spccific CD8+ Tc cells do not produce IFN-γ and are furthermore suppressed by IFN-γ. 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.
- Subjects
CANCER cells; T cells; CARCINOGENESIS; PLASMACYTOMA; LYMPHOCYTES
- Publication
Scandinavian Journal of Immunology, 1996, Vol 43, Issue 4, p421
- ISSN
0300-9475
- Publication type
Article
- DOI
10.1046/j.1365-3083.1996.d01-56.x