Importance of Lyt 2+ T-Cells in the Curative Effectiveness of a Low Dose of Melphalan for Mice Bearing a Large MOPC-315 Tumor1

We have previously demonstrated that the curative effectiveness of a low dose (2.5 mg/kg) of melphalan (i.-phenylalanine mustard; L-PAM) for mice bearing a large s.c. (approximately 20 mm in diameter) MOPC315 tumor and extensive métastases requires the participation of T-celldependent antitumor immunity in tumor eradication (S. Ben-Efraim et al.. Cancer luminimi. Immunother., 15: 101-107, 1983). Here we show that the Lyt 2* T-cells, and not the I .VI4' T-cells, participate in the cure of such tumor-bearing mice by a low dose of L-PAM. Specifically, depletion of Lyt 2* T-cells from mice bearing a large MOPC-315 tumor by treatment with monoclonal anti-Lyt 2.2 antibody abolished the curative effectiveness of the low dose of drug. In contrast, depletion of I TI 4* I cells from mice bearing a large MOPC-315 tumor by treatment with monoclonal unti-L.Tl 4 antibody did not reduce significantly the curative effectiveness of the low dose of drug. HistolÃ3gica! examination of tumor nodules on various days following low-dose L-PAM therapy revealed widespread lymphocytic infiltration by Day 5 following the chemother apy, and this infiltration was drastically reduced when the L-PAMtreated tumor bearers were treated with either anti-Thy 1.2 or anti-Lyt 2.2 antibody but not with anti-L3T4 antibody. The antitumor immunity exhibited by Lyt 2* T-cells derived from mice which were in the process of eradicating a large MOPC-315 tumor following low-dose L-PAM therapy was exploited successfully to confer systemic antitumor immunity to mice bearing a barely palpable tumor. Specifically, the adoptively transferred Lyt 2+ splenic T-cells, in conjunction with a subcurative dose of L-PAM, brought about the cure of most mice. The Lyt 1* splenic Tcells from L-PAM-treated MOPC-315 tumor bearers were also found to be capable of exerting a direct potent lytic effect against MOPC-315 tumor cells in an antigen-specific manner. Thus, it is conceivable that the direct cytotoxic activity of Lyt 2+ T-cells for MOPC-315 tumor cells is responsible, at least in part, for the ability of the Lyt T T-cells from I PAM-treated MOPC-315 tumor bearers to bring about the eradication of the tumor burden not eradicated through the direct antitumor effects of the low dose of drug.