Summary
This study was designed to investigate the nature of lymphocyte reactivity to soluble tumor antigens with respect to the kinetics of the reactivity, the responding cell type, and the role of accessory cells, within a syngeneic system. BALB/c mice were inoculated with 1×106 viable cells of sygeneic MTV-induced mammary tumors. Assessment of proliferative activity of spleen cells of these animals by DNA synthesis (3H-thymidine incorporation in vitro) indicated a biphasic response to stimulation by 200 μg of a syngeneic perchloric acid (PCA)-soluble extract (AMMT) of the tumor over a 25-day period, with peak activities at days 13 and 19 post inoculation. The response was predominantly T-cell-mediated. Splenic macrophage population rose from less than 2% of total spleen cells by day 25 without any appreciable change in the T or B cell population. Depletion of spleen cells of macrophages abolished the first peak activity (at day 13) but significantly enhanced the second (at day 19). Reconstitution of the depleted cells with macrophages prepared from peritoneal exudates of tumor-bearing or normal mice restored the responses to undepleted values, thus indicating an accessory role for macrophages in these responses. These results provide new data which should contribute to a better understanding of the tumor-host relationship.
Similar content being viewed by others
References
Adler HL, Roessler EB (1964) Introduction to probability and statistics. Freeman, San Francisco
Banjo C, Gold P, Gehrke CW, Freedman SO, Krupey J (1974a) Preparation and isolation of immunologically active glycopeptides from carcinoembryonic antigen (CEA). Int J Cancer 13:151
Banjo C, Schuster J, Gold P (1974b) Intramolecular heterogeneity of carcinoembryonic antigen. Cancer Res 34:2114
Beverly PCL (1978) T effector cells. In: Castro JE (ed) Immunological aspects of cancer. University Park Press, Baltimore, p 101
Connally KM, Elgert KD (1979) Reversal of macrophage-augmented MLR reactivity by tumor-induced splenic suppressor T-cells and their soluble factors. Cell Immunol 44:99
Connally KM, Elgert KD (1979) Regulation of T-cell mixed lymphocyte reactivity: Demonstration of enhancing and inhibitory activity in tumor-bearing host macrophage supernatants. Cell Immunol 45:94
Elgert D, Farrar WL (1978) Suppressor cell activity in tumor-bearing mice. I. Dualistic inhibition by suppressor T lymphocyte and macrophages. J Immunol 120:1345
Glaser M, Herberman RB, Kirchner H, Djue JY (1974) Study of the cellular immune response to Gross virus-induced lymphoma by the mixed lymphocyte-tumor interaction. Cancer Res 34:2165
Gold P, Freedman SO (1965) Specific carcinoembryonic antigen of the human digestive system. J Exp Med 122:467
Gold JM, Banjo C, Freedman SO, Gold P (1973) Studies of the intramolecular heterogeneity of CEA. J Immunol 111:1872
Green MI, Perry LL (1978) Regulation of immune response to tumor antigen. VI. Differential specificities of suppressor T-cells or their products and effector T-cells. J Immunol 121:2363
Handwerger BS, Schwartz RH (1974) Separation of murine lymphoid cells using nylon wool columns: Recovery of the B-cell enriched population. Transplantation 18:544
Hansen HJ, Snyder JJ, Miller E, Vandevoorde JP, Miller N, Hines LR, Burns JJ (1974) Carcinoembryonic antigen (CEA) assay. Hum Pathol 5:138
Heppner GH (1972) Blocking antibodies and enhancement. Ser Haemat 5:41
Heppner GH (1973) Colony inhibition and microcytotoxicity assay methods for measuring cell-mediated and associated antibody immunity in vitro. Methods in Cancer Research 8:32
Herberman RB, Campbell DA Jr, Oldham RK, Bonnard GD, Ting Chou-Chik, Holden HT, Glaser M, Djeu J, Oehler R (1976) Immunogenicity of tumor antigens. Ann NY Acad Sci 276:26
Julius MH, Simpson E, Herzenberg LA (1973) A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol 3:645
Kirchner H, Chused TM, Herberman RB, Holden HT, Laurin DH (1974) Evidence of suppressor cell activity in spleens of mice bearing primary tumors induced by Maloney sarcoma virus. J Exp Med 139:1473
Laing CA, Bekesi JG, Heppner GH (1978a) Tumor antigens: Biological activity of components of soluble antigens of MTV-induced mammary tumors. Cancer Immunol Immunother 4:5
Laing CA, Bekesi JG, Holland JF (1978b) Inhibition of PHA-induced agglutination and blastogenesis of mouse splenic lymphocytes in vitro by syngeneic tumor bearer sera. In: Nieburgs HE (ed) Prevention and detection of cancer, part 2, vol 1. Dekker, New York, p 281
Lopez DM, Sigel MM (1975) Correlation of tumor growth and cell-mediated immune responses of mice bearing mammary tumors following surgical procedures. J Reticuloendothel Soc 18:305
Nelson DS (1973) Production by stimulated macrophages of factors depressing lymphocyte transformation. Nature 246:306
Pick E, Cohen S, Oppenhein J (1979) The lymphokine concept. In: Cohen S et al. (eds) Biology of the lymphokines. Academic Press, New York, p 1
Price MR, Robins R (1978) Circulating factors modifying cell-mediated immunity in experimental neoplasia. In: Castro JE (ed) Immunological aspects of cancer. University Park Press, Baltimore, p 155
Thompson DM, Krupey J, Freedman SO (1969) The radioimmunoassay of carcinoembryonic antigen of the human digestive system. Proc Natl Acad Sci USA 64:161
Tigelaar RE, Asofsky R (1973) Synergy among lymphoid cells mediating the graft-versus-host response. J Exp Med 137:239
Ungaard G (1978) Immunosuppressive effect of human macrophages. II. Influence of macrophages on the kinetics of DNA, RNA and protein synthesis in PHA-stimulated lymphocytes. Acta Pathol Microbiol Scand [Sect. C] 86:187
Varesio L, Holden HT (1980) Regulation of lymphocyte activation: Macrophage-dependent suppression of T lymphocyte protein synthesis. J Immunol 125:1694
Yam LT, Li CY, Crosby WH (1971) Cytochemical identification of monocytes and granulocytes. Am J Pathol 55:283
Yoshinaga M, Yoshinaga A, Waksman BH (1972) Regulation of lymphocyte responses in vitro. I. Regulatory effect of macrophages and thymus-dependent (T) cells on the responses of thymus-independent (B) lymphocytes to endotoxin. J Exp Med 135:956
Youdim S (1979) Enhancing and suppressive effects of macrophages on T-lymphocyte stimulation in vitro. Cell Immunol 45:377
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Laing, C.A. Kinetics of the reactivity of subpopulations of spleen cells of mice bearing virus-induced mammary tumors to syngeneic antigenic extracts in vitro. Cancer Immunol Immunother 13, 98–104 (1982). https://doi.org/10.1007/BF00205308
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00205308