Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Kinetics of the reactivity of subpopulations of spleen cells of mice bearing virus-induced mammary tumors to syngeneic antigenic extracts in vitro

Supportive and suppressive effects of macrophages

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.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Adler HL, Roessler EB (1964) Introduction to probability and statistics. Freeman, San Francisco

  2. 2.

    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

  3. 3.

    Banjo C, Schuster J, Gold P (1974b) Intramolecular heterogeneity of carcinoembryonic antigen. Cancer Res 34:2114

  4. 4.

    Beverly PCL (1978) T effector cells. In: Castro JE (ed) Immunological aspects of cancer. University Park Press, Baltimore, p 101

  5. 5.

    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

  6. 6.

    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

  7. 7.

    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

  8. 8.

    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

  9. 9.

    Gold P, Freedman SO (1965) Specific carcinoembryonic antigen of the human digestive system. J Exp Med 122:467

  10. 10.

    Gold JM, Banjo C, Freedman SO, Gold P (1973) Studies of the intramolecular heterogeneity of CEA. J Immunol 111:1872

  11. 11.

    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

  12. 12.

    Handwerger BS, Schwartz RH (1974) Separation of murine lymphoid cells using nylon wool columns: Recovery of the B-cell enriched population. Transplantation 18:544

  13. 13.

    Hansen HJ, Snyder JJ, Miller E, Vandevoorde JP, Miller N, Hines LR, Burns JJ (1974) Carcinoembryonic antigen (CEA) assay. Hum Pathol 5:138

  14. 14.

    Heppner GH (1972) Blocking antibodies and enhancement. Ser Haemat 5:41

  15. 15.

    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

  16. 16.

    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

  17. 17.

    Julius MH, Simpson E, Herzenberg LA (1973) A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol 3:645

  18. 18.

    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

  19. 19.

    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

  20. 20.

    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

  21. 21.

    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

  22. 22.

    Nelson DS (1973) Production by stimulated macrophages of factors depressing lymphocyte transformation. Nature 246:306

  23. 23.

    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

  24. 24.

    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

  25. 25.

    Thompson DM, Krupey J, Freedman SO (1969) The radioimmunoassay of carcinoembryonic antigen of the human digestive system. Proc Natl Acad Sci USA 64:161

  26. 26.

    Tigelaar RE, Asofsky R (1973) Synergy among lymphoid cells mediating the graft-versus-host response. J Exp Med 137:239

  27. 27.

    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

  28. 28.

    Varesio L, Holden HT (1980) Regulation of lymphocyte activation: Macrophage-dependent suppression of T lymphocyte protein synthesis. J Immunol 125:1694

  29. 29.

    Yam LT, Li CY, Crosby WH (1971) Cytochemical identification of monocytes and granulocytes. Am J Pathol 55:283

  30. 30.

    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

  31. 31.

    Youdim S (1979) Enhancing and suppressive effects of macrophages on T-lymphocyte stimulation in vitro. Cell Immunol 45:377

Download references

Author information

Rights and permissions

Reprints 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

Download citation

Keywords

  • Perchloric Acid
  • Mammary Tumor
  • Spleen Cell
  • Peak Activity
  • Post Inoculation