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Tumor-specific L3T4+ and Lyt-2+ lymphocytes in mice primed to mutagenized cell variants
R Bianchi1, M C Fioretti, U Grohmann
1Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Abstract:
We have investigated the tumor-specific reactivity of different T-cell subsets from mice primed with clonal variants of L5178Y and P815 cells treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In both tumor systems, anti-parental tumor immunity and protection against non-immunogenic clones were only induced by vaccinating the hosts with highly immunogenic cell variants, and the effect correlated with the detection of TATA-specific delayed-type hypersensitivity (DTH) reactions. The footpad reaction was transferable with spleen cell populations from immunized mice, and enrichment of splenic lymphocytes in L3T4+ but not Lyt-2+ lymphocytes increased the footpad swelling. Unfractionated spleen cell populations from immunized mice released high amounts of IL-2 and IFN-gamma in vitro in response to parental antigens. Purified L3T4+ and Lyt-2+ lymphocytes also produced IFN-gamma when incubated in vitro with the parental tumors and accessory cells. It is suggested that the mechanisms of anti-parental tumor immunity induced by MNNG-treated variants may be similar to those described previously for triazene-xenogenized L5178Y/DTIC cells, and may involve induction of a tumor-specific DTH reaction and IFN-gamma-mediated stimulation of non-specific tumoricidal effects.
Insights
Highly immunogenic tumor variants induced anti-tumor immunity and delayed-type hypersensitivity (DTH) reactions. This immunity involved T-cell subsets and cytokine production, suggesting a mechanism for non-specific tumoricidal effects.
Area of Science:
- Immunology
- Cancer Research
- Cell Biology
Background:
- Tumor variants can elicit specific immune responses.
- N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment can modify tumor cell immunogenicity.
Purpose of the Study:
- To investigate T-cell subset reactivity against tumor variants.
- To understand the mechanisms of anti-tumor immunity induced by MNNG-treated cells.
Main Methods:
- Priming mice with MNNG-treated L5178Y and P815 tumor variants.
- Assessing delayed-type hypersensitivity (DTH) reactions.
- Transferring spleen cells and analyzing T-cell subsets (L3T4+, Lyt-2+).
- Measuring cytokine production (IL-2, IFN-gamma) in vitro.
Main Results:
- Highly immunogenic variants induced anti-parental tumor immunity and DTH.
- Immunity correlated with TATA-specific DTH reactions.
- Spleen cell transfer mediated footpad reactions, enhanced by L3T4+ cells.
- Immunized T-cells produced IL-2 and IFN-gamma in response to tumor antigens.
Conclusions:
- MNNG-treated tumor variants can induce specific anti-tumor immunity.
- Tumor-specific DTH reactions and IFN-gamma are likely key mechanisms.
- The findings suggest a pathway for non-specific tumoricidal effects mediated by T-cells.