Importance of Lyt-2+ T-cells in the resistance of melphalan-cured MOPC-315 tumor bearers to a challenge with MOPC-315 tumor cells.
We have previously shown that mice bearing a large MOPC-315 tumor can be cured by a low dose of melphalan (L-phenylalanine mustard; L-PAM) if T-cell-dependent antitumor immunity also aids in tumor eradication (S. Ben-Efraim et al., Cancer Immunol. Immunother., 15: 101-107, 1983). Here we describe the phenotype of the T-cells that are responsible for the potent antitumor immunity exhibited by the L-PAM cured MOPC-315 tumor bearers. Initially, we identified the subset of T-cells responsible for the ability of spleen cells from L-PAM-cured MOPC-315 tumor bearers to neutralize tumor growth in the local adoptive transfer assay. The tumor-neutralizing activity of spleen cells from L-PAM-cured tumor bearers was drastically reduced when the spleen cells were depleted either in vitro or in vivo of Lyt-2+ cells. On the other hand, the tumor-neutralizing activity of spleen cells from L-PAM-cured MOPC-315 tumor bearers was not reduced, but actually enhanced, when the spleen cells were depleted either in vitro or in vivo of L3T4+ cells. The Lyt-2+ T-cells, and not the L3T4+ T-cells, were also found to be important for the ability of the intact L-PAM-cured MOPC-315 tumor bearers to reject a challenge with MOPC-315 tumor cells. Specifically, treatment of L-PAM-cured MOPC-315 tumor bearers with monoclonal anti-Lyt-2.2 antibody drastically reduced the ability of the mice to reject the tumor challenge. In contrast, treatment of the L-PAM-cured MOPC-315 tumor bearers with monoclonal anti-L3T4 antibody did not interfere with the ability of the mice to reject the tumor challenge, yet the same protocol of anti-L3T4 antibody treatment abolished the ability of splenic T-cells to provide help for the generation of a primary T-cell-dependent antibody response. The resistance of the L-PAM-cured MOPC-315 tumor bearers to challenge with MOPC-315 tumor cells was also dependent on the participation of carrageenan-sensitive effector cells, most likely macrophages, in tumor eradication. However, the immunity mediated by the T-cells, independent of carrageenan-sensitive effector cells, was extremely powerful and sufficient for the rejection of a tumor challenge with at least 300-fold, and possibly even 3000-fold, the minimal lethal dose of MOPC-315 tumor cells for 100% of normal mice.(ABSTRACT TRUNCATED AT 400 WORDS)
Barker
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Department of Microbiology and Immunology, University of Illinois, Chicago 60612.
Mokyr
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000950:Antigens, Ly / Q000276:immunology*; D002351:Carrageenan / Q000494:pharmacology; D005260:Female; D006084:Graft Rejection; D007111:Immunity, Cellular; D008558:Melphalan / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D002351:Carrageenan; D008558:Melphalan