This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mokyr, M. B. Articles by Pyle, J. M. Search for Related Content PubMed PubMed Citation Articles by Mokyr, M. B. Articles by Pyle, J. M.

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

Department of Microbiology and Immunology, University of Illinois at Chicago Health Sciences Center, Chicago, Illinois 60612 [M. B. M., E. B., L. M. W., B. Y. T.], and Department of Pathology, Rush Medical College, Chicago, Illinois 60612 [J. M. P.]

We have previously demonstrated that the curative effectiveness of a low dose (2.5 mg/kg) of melphalan (L-phenylalanine mustard; L-PAM) for mice bearing a large s.c. (approximately 20 mm in diameter) MOPC-315 tumor and extensive metastases requires the participation of T-cell-dependent antitumor immunity in tumor eradication (S. Ben-Efraim et al., Cancer Immunol. Immunother., 15: 101–107, 1983). Here we show that the Lyt 2⁺ T-cells, and not the L3T4⁺ 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 L3T4⁺ T-cells from mice bearing a large MOPC-315 tumor by treatment with monoclonal anti-L3T4 antibody did not reduce significantly the curative effectiveness of the low dose of drug. Histological examination of tumor nodules on various days following low-dose L-PAM therapy revealed widespread lymphocytic infiltration by Day 5 following the chemotherapy, and this infiltration was drastically reduced when the L-PAM-treated 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 2⁺ splenic T-cells 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 2⁺ T-cells from L-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.

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

² Supported by Career Development Award CA-01350 from the National Cancer Institute. To whom requests for reprints should be addressed.

³ In partial fulfillment of the requirements for the Doctor of Philosophy degree.

Received 1/18/89. Revised 4/10/89. Accepted 5/19/89.

This article has been cited by other articles:

				V. M. Jovasevic and M. B. Mokyr Melphalan-Induced Expression of IFN-{beta} in MOPC-315 Tumor-Bearing Mice and Its Importance for the Up-Regulation of TNF-{alpha} Expression J. Immunol., November 1, 2001; 167(9): 4895 - 4901. [Abstract] [Full Text] [PDF]

				M. Donepudi, P. Raychaudhuri, J. A. Bluestone, and M. B. Mokyr Mechanism of Melphalan-Induced B7-1 Gene Expression in P815 Tumor Cells J. Immunol., June 1, 2001; 166(11): 6491 - 6499. [Abstract] [Full Text] [PDF]

				D. K. Sojka, M. Donepudi, J. A. Bluestone, and M. B. Mokyr Melphalan and Other Anticancer Modalities Up-Regulate B7-1 Gene Expression in Tumor Cells J. Immunol., June 15, 2000; 164(12): 6230 - 6236. [Abstract] [Full Text] [PDF]

				V. V. Kalinichenko, M. B. Mokyr, L. H. Graf Jr., R. L. Cohen, and D. A. Chambers Norepinephrine-Mediated Inhibition of Antitumor Cytotoxic T Lymphocyte Generation Involves a {beta}-Adrenergic Receptor Mechanism and Decreased TNF-{alpha} Gene Expression J. Immunol., September 1, 1999; 163(5): 2492 - 2499. [Abstract] [Full Text] [PDF]

				M. B. Mokyr, T. V. Kalinichenko, L. Gorelik, and J. A. Bluestone Importance of the B7-2 Molecule for Low Dose Melphalan-Induced Acquisition of Tumor-Eradicating Immunity by Mice Bearing a Large MOPC-315 Tumor J. Immunol., February 15, 1998; 160(4): 1866 - 1874. [Abstract] [Full Text] [PDF]