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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‐γ
Author(s) -
PAUELS H.G.,
SPECHT C.,
BECKER C.,
KÖLSCH E.
Publication year - 1996
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1996.d01-56.x
Subject(s) - cytotoxic t cell , cd8 , biology , t lymphocyte , immunology , microbiology and biotechnology , cancer research , in vitro , immune system , biochemistry
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‐specific 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.