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Importance of Lyt-2⁺ T-Cells in the Resistance of Melphalan-cured MOPC-315 Tumor Bearers to a Challenge with MOPC-315 Tumor Cells¹

Department of Microbiology and Immunology, University of Illinois at Chicago Health Sciences Center, Chicago, Illinois 60612

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. Consequently, in order to illustrate the importance of carrageenan-sensitive effector cells in the resistance of the L-PAM-cured MOPC-315 tumor bearers to tumor challenge, it was necessary to increase the challenge inoculum to 30,000-fold the minimal lethal dose of tumor cells so as to surpass the challenge inoculum that can be rejected by T-cell-dependent immunity in the absence of carrageenan-sensitive effector cells.

¹ Supported by Research Grant IM-435 from the American Cancer Society and Research Grant CA-35761 from the National Cancer Institute.

² In partial fulfillment of the requirements for the Ph.D. degree.

³ To whom requests for reprints should be addressed.

Received 3/18/88. Revised 5/17/88. Accepted 5/27/88.