Abstract
In vitro treatment with 2 μg/2×106 cells melphalan (l-PAM: l-phenylalanine mustard) significantly decreased the total number of T lymphocytes from peripheral blood (PBL) of healthy human donors and of the OKT4 population (precursor suppressor/helper/inducer) T cells as defined by monoclonal antibodies OKT3 and OKT4, respectively. No changes in the OKT+8lymphocyte population (cytotoxic/mature suppressor cells) were observed following the same treatment. Preincubation of PBL with l-PAM at concentrations that do not affect the rate of DNA synthesis in PHA-stimulated lymphocytes inhibited the generation of T suppressor lymphocytes by ConA, as shown by their effect on PHA stimulation. Treatment of allogeneic PBL with l-PAM had no effect on mature suppressor T cells already induced by Con A, as shown by incubation of PBL with l-PAM after incubation with ConA.
Keywords: Monoclonal Antibody, Melphalan, Suppressor Cell, Selective Effect, Lymphocyte Population
References
- 1.Ben-Efraim S, Bocian RC, Mokyr MB, Dray S. Increase in the effectiveness of melphalan therapy with progression of MOPC-315 plasmacytomas tumor growth. Cancer Immunol Immunother. 1983;15:101. doi: 10.1007/BF00199699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Boyum A. Separation of leukocytes from blood and bone marrow. Scand J Clin Lab Invest. 1968;21:77. [PubMed] [Google Scholar]
- 3.Carpenter JT, Maddox WA. Melphalan adjuvant therapy in breast cancer. Lancet. 1983;II:450. doi: 10.1016/s0140-6736(83)90407-5. [DOI] [PubMed] [Google Scholar]
- 4.Chassoux DM, Gotch FM, MacLennan ICM. Analysis of synergy between cyclophosphamide therapy and immunity against a mouse tumor. Br J Cancer. 1978;38:211. doi: 10.1038/bjc.1978.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Cornbleet MA, McElwain TJ, Kumar PJ, Filshie J, Selby P, Carter RL. Treatment of advanced malignant melanoma with high-dose melphalan and autologous bone marrow transplant. Br J Cancer. 1983;48:329. doi: 10.1038/bjc.1983.196. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Diamantstein T, Klos M, Hahn H, Kaufman SHE. Direct in vitro evidence for different susceptibilities to 4-hydroxyperoxy-cyclosphosphamide of antigen-primed T cells regulating humoral and cell-mediated immune responsens to sheep erythrocyes: a possible explanation for the inverse action of cyclophosphamide on humoral and cell-mediated immune responses. J Immunol. 1981;126:1717. [PubMed] [Google Scholar]
- 7.Hengst JCD, Mokyr MB, Dray S. Cooperation between cyclophosphamide tumoricidal activity and host antitumor immunity in the cure of mice bearing large MOPC-315 tumors. Cancer Res. 1981;41:2163. [PubMed] [Google Scholar]
- 8.Klayman A, Drucker I, Manor J, Ben-Efraim S. In vitro effects of 4-hydroperoxycyclophosphamide on concanavalin A-induced human suppressor T cells. Cancer Immunol Immunother. 1984;18:113. doi: 10.1007/BF00205744. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.L'Age-Stehr J, Diamantstein T. Induction of autoreactive T lymphocytes and their suppressor cells by cyclophosphamide. Nature. 1978;271:663. doi: 10.1038/271663a0. [DOI] [PubMed] [Google Scholar]
- 10.MacKey IK, Goodyear MDE, Riglar C, Penschow J. Effect on natural killer and antibody-dependent cellular cytotoxicity of adjuvant cytotoxic chemotherapy including melphalan in breast cancer. Cancer Immunol Immunother. 1983;16:98. doi: 10.1007/BF00199239. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Maguire H, Berd D, Engstrom P, Manstrangelo M. Cyclophosphamide increases the acquisition of T cell immunity in patients with melanoma and colo-rectal cancer. Proc AACR. 1981;22:279. [Google Scholar]
- 12.McElwain TJ, Powles RL. High-dose intravenous melphalan for plasma cell-leukemia and myeloma. Lancet. 1983;II:822. doi: 10.1016/s0140-6736(83)90739-0. [DOI] [PubMed] [Google Scholar]
- 13.Mokyr MB, Hengst JCD, Dray S. Role of antitumor immunity in cyclophosphamide-induced rejection of subcutaneous nonpalpable MOPC-315 tumors. Cancer Res. 1982;42:974. [PubMed] [Google Scholar]
- 14.North RJ. Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells. J Exp Med. 1982;55:1063. doi: 10.1084/jem.155.4.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Ozer H, Cowens JW, Colvin M, Nussbaum-Blumenson A, Sheedy D. In vitro effects of 4-hydroperoxycyclophosphamide on human immuno-regulatory T subset function. I. Selective effects on lymphocyte function in T-B cell collaboration. J Exp Med. 1982;155:276. doi: 10.1084/jem.155.1.276. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Takada S, Ueda Y, Murukawa Y, Suzuki N. Functional heterogeneity among Concanavalin A-activated OKT4+ and OKT8 cells by using autologous erythrocyte rosette technique. J Clin Invest. 1983;72:2060. doi: 10.1172/JCI111171. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Thomas Y, Rogozinski L, Irigoyen OH, Shen HH, Talle MA, Goldstein G, Chess L. Functional analysis of human T cell subsets defined by monoclonal antibodies. V. Suppressor cells within the activated OKT4+ population belong to a distinct subset. J Immunol. 1983;128:1386. [PubMed] [Google Scholar]