CD8+ tumor-specific Tc cells primed in vivo or in vitro against the BALB/c plasmacytoma ADJ-PC-5 use the same TcR V beta families but display distinct TC1 or TC2 characteristics.
The involvement of counteractive CD8+ T cell subsets in tumor-specific unresponsiveness was analyzed in a syngeneic murine tumor model. CD8+ cytotoxic T cells against the IL-10 producing BALB/c plasmacytoma ADJ-PC-5 can be easily induced in vitro, in a primary syngeneic mixed lymphocyte tumor cell culture (MLTC), or in vivo, by repeated immunization of syngeneic BALB/c mice with high doses of X-irradiated ADJ-PC-5 tumor cells. Long term cultivated CD8+ ADJ-PC-5-specific Tc lines use either TcR of the V beta 6 or V beta 8.1/8.2 type, irrespective if the lines were derived from a primary MLTC or from immunized mice. While most of the Tc lines produce type-1 cytokines (IFN-gamma, no IL-4) upon stimulation, at least two of them, which were derived from a primary MLTC, display a type-2 cytokine spectrum (IL-4, no IFN-gamma). The primary in vitro Tc response against ADJ-PC-5 cells shows characteristics of a TC2 response: CD8+ Tc cells which are induced in a primary MLTC do not produce IFN-gamma, and the tumor-specific Tc response is enhanced by IL-4 but suppressed by IFN-gamma or IL-12. In contrast, ADJ-PC-5-specific CD8+ Tc cells from immunized mice are IFN-gamma producing TC1 cells. Since the primary in vitro Tc response against the tumor is suppressed even by lowest numbers of irradiated ADJ-PC-5-specific TC1 cells via IFN-gamma, these TC1 cells behave similar to a previously described regulatory subset of IFN-gamma producing CD8+ T cells, which are induced during early stages of ADJ-PC-5 tumorigenesis and inhibit the induction of a tumor-specific Tc response from naive BALB/c spleen cells in vitro.
Becker
C
C
Institute of Immunology, University of Münster, Germany.
Kölsch
E
E
Pauels
H G
HG
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D005260:Female; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D005810:Multigene Family / Q000276:immunology; D010954:Plasmacytoma / Q000276:immunology* / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification* / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007166:Immunosuppressive Agents; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma