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Prevention by the MER tubercle bacillus fraction of immunosuppression induced by cancer chemotherapeutic agents

II. Contact hypersensitivity in guinea pigs and mice treated with cyclophosphamide

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Summary

Contact hypersensitivity (CH) to 2,4-dinitro-1-fluorobenzene (DNFB) was induced in guinea pigs and mice by DNFB skin application. Development of CH was suppressed in both species either by cyclophosphamide (CY) treatment after sensitization or by single intravenous injection of dinitrobenzene-sulfonate (DNBS) before sensitization (hapten-induced tolerance). Additional treatment schedules were employed in guinea pigs, with the following results: Suppression of CH by injection of DNBS concomitant with sensitization; abrogation of hapten-induced tolerance by administration of CY before sensitization; and potentiation of CH skin reactivity by administration of CY before sensitization.

Pretreatment by two injections of the methanol extraction residue (MER) tubercle bacillus fraction restored significantly the ability of CY treated animals to respond to DNFB sensitization. In contrast, administration of MER either by one injection before sensitization, concomitant with DNFB, or after sensitization did not prevent immunosuppression by CY.

MER treatment was not effective in reversing hapten-induced tolerance in mice, and had only an occasional effect on this process in guinea pigs. Abrogation of hapten-induced tolerance and potentiation of DNFB sensitization by CY in guinea pigs were also not influenced by MER treatment.

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References

  • Asherson, G. L., Allwood, G. G., Mayhew, B.: Contact sensitivity in the mouse. XI. Movement of T blasts in the draining lymph nodes to sites of inflammation. Immunology 25, 485 (1973)

    Google Scholar 

  • Asherson, G. L., Zembala, M.: Suppression of contact sensitivity of T cells in the mouse. I. Demonstration that suppressor cells act on the effector stage of contact sensitivity; and their induction following in vitro exposure to antigen. Proc. R. Soc. Lond. B 187, 329 (1974)

    Google Scholar 

  • Bach, J. F.: The mode of action of immunosuppressive agents. In: Frontiers of Biology, Vol. 41. Neuberger, A., Tatum, E. L. (eds.). Amsterdam: North Holland 1975

    Google Scholar 

  • Ben-Efraim, S.: MER: Effects and mechanisms of action. In: International Encyclopedia of Pharmacology and Therapeutics “Modulation of Immunity”. London: Pergamon Press (in press) 1977

    Google Scholar 

  • Claman, H. N.: Tolerance and contact sensitivity to DNFB in mice. V. Induction of tolerance with DNP compounds and with free and membrane-associated DNFB. J. Immunol. 116, 704 (1976)

    Google Scholar 

  • Gallily, R., Yagel, S., Weiss, D. W.: Potentiated Lysosomal Enzyme Bacteriostatic and Bactericidal Activities of Peritoneal Macrophages of Mice Treated with MER Fraction of Tubercle bacilli. Proc. 7th International Congress of the Reticuloendothelial System on Health and Disease, p. 351. Reichert, G. M., Escobar, M. R., Friedman, H. (eds.). New York: Plenum Press 1976

    Google Scholar 

  • Gery, I., Baer, A., Stupp, Y., Weiss, D. W.: Further studies on the effects of the methanol extraction residue fraction of tubercle bacilli on lymphoid cells and macrophages. Isr. J. Med. Sci. 10, 984 (1974)

    Google Scholar 

  • Izak, G., Stupp, Y., Manny, N., Zajcek, G., Weiss, D. W.: The Immune Response in Acute Myelocytic Leukemia. The Effect of MER on T- and B-cell Functions and Their Relation to the Course of the Disease. Proc. International Symposium on Malignant Proliferative Diseases. Jerusalem, July 1976. Izak, G. (ed.). New York: Academic Press 1977

    Google Scholar 

  • Kuperman, O., Feigis, M., Weiss, D. W.: Reversal by the MER tubercle bacillus fraction of the suppressive effects of heterologous antilymphocytic serum (ALS) on the allograft reactivity of mice. Cell. Immunol. 8, 424 (1973)

    Google Scholar 

  • Lagrange, P. H., Mackaness, G. B., Miller, T. E.: Potentiation of T-cell-mediated immunity by selective suppression of antibody formation with cyclophosphamide. J. Exp. Med. 139, 1529 (1974)

    Google Scholar 

  • Miller, A. E., Levis, W. R.: Lymphocyte transformation during dinitrochlorobenzene contact sensitization: an in vitro-in vivo evaluation of the primary immune response in man. J. Clin. Invest. 52, 1925 (1973a)

    Google Scholar 

  • Miller, A. E., Levis, W. R.: Studies on the contact sensitization of man with simple chemicals. I. Specific lymphocyte transformation in response to dinitrochlorobenzene sensitization. J. Invest. Dermatol. 61, 261 (1973b)

    Google Scholar 

  • Parrot, D. W. V. de, Sousa, M. A. B., Fachet, J., Wallis, V., Leuchars, E., Davies, A. J. S.: The response of normal thymectomized and reconstituted mice in contact sensitivity. Clin. Exp. Immunol. 7, 387 (1970)

    Google Scholar 

  • Phanuphak, P., Moorhead, J. W., Claman, H. N.: Tolerance and contact sensitivity to DNFB in mice. I. In vivo detection by ear swelling and correlation with in vitro cell stimulation. J. Immunol. 112, 115 (1974a)

    Google Scholar 

  • Phanuphak, P., Moorhead, J. W., Claman, H. N.: Tolerance and contact sensitivity to DNFB in mice. II. Specific in vitro stimulation with hapten, 2,4-dinitrobenzene sulfonic acid (DNB SO3Na). J. Immunol. 112, 849 (1974b)

    Google Scholar 

  • Phanuphak, P., Moorhead, J. W., Claman, H. N.: Tolerance and contact sensitivity to DNFB in mice. IV. Desensitization as a manifestation of increased proliferation of sensitized cells. J. Immunol. 114, 1147 (1975)

    Google Scholar 

  • Polak, L.: Suppressor cells in different types of unresponsiveness to DNCB contact sensitivity in guinea-pigs. Clin. Exp. Immunol. 19, 543 (1975)

    Google Scholar 

  • Polak, L.: Studies on the role of suppressor cells in specific unresponsiveness to DNCB. Immunology 31, 425 (1976)

    Google Scholar 

  • Polak, L., Turk, J. L.: Reversal of immunological tolerance by cyclophosphamide through inhibition of suppressor cell activity. Nature (Lond.) 249, 654 (1974)

    Google Scholar 

  • Polak, L., Frey, J. R., Turk, J. L.: Dissociation between lymph node and peripheral reactivity in immunological unresponsiveness to DNCB. Immunology 25, 451 (1973)

    Google Scholar 

  • Polak, L., Geleick, H., Turk, J. L.: Reveral by cyclohosphamide of tolerance in contact sensitization. Tolerance induced by prior feeding with DNCB. Immunology 28, 939 (1975)

    Google Scholar 

  • Pritchard, H., Micklem, H. S.: Immune responses in congenitally thymusless mice. I. Absence of response to oxazolone. Clin. Exp. Immunol. 10, 151 (1972)

    Google Scholar 

  • Stockman, G. D., Heim, L. R., South, M. A., Trentin, J. J.: Differential effects of cyclophosphamide on the B and T cell compartments of adult mice. J. Immunol. 110, 277 (1973)

    Google Scholar 

  • Turk, J. L.: Studies on the mechanism of action of methorexate and cyclophosphamide on contact sensitivity in the guinea pig. Int. Arch. Allergy 24, 191 (1964)

    Google Scholar 

  • Turk, J. L., Parker, D., Poulter, L. W.: Functional aspects of the slectiveevedepletion of lymphoid tissue by cyclophosphamide. Immunology 23, 493 (1972)

    Google Scholar 

  • Turk, J. L., Polak, L., Parker, D.: Control mechanism in delayed-type hypersensitivity. Brit. Med. Bull. 32, 165 (1976)

    Google Scholar 

  • Weiss, D. W.: MER and other mycobacterial fractions in the immunotherapy of cancer. In: Symposium on immunotherapy in malignant disease. Med. Clin. North America 60, 473 (1976)

    Google Scholar 

  • Weiss, D. W., Yashphe, D. J.: Nonspecific stimulation of antimicrobial and antitumor resistance and of immunological responsiveness by the MER fraction of tubercle bacilli. In: Dynamic Aspects of Host-Parasite Relationships, Vol. 1, p. 163. Zuckerman, A., Weiss, D. W. (eds.). New York: Academic Press 1973

    Google Scholar 

  • Zembala, M., Asherson, G. L.: The role of T cells in the passive transfer of contact sensitivity and their occurrence in the bone marrow. Eur. J. Immunol. 3, 677 (1973a)

    Google Scholar 

  • Zembala, M., Asherson, G. L.: Depression of the T cell phenomenon of contact sensitivity by T cells from unresponsive mice. Nature (Lond.) 244, 227 (1973b)

    Google Scholar 

  • Zembala, M., Asherson, G. L.: The effect of cyclophosphamide and irradiation on cells which suppress contact sensitivity in the mouse. Clin. Exp. Immunol. 23, 554 (1976)

    Google Scholar 

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Authors and Affiliations

  1. Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Chava Zimber & Shlomo Ben-Efraim

  2. Lautenberg Center for General and Tumor Immunology, Hebrew University, Hadassah Medical School, Jerusalem, Israel

    David M. Weiss

Authors
  1. Chava Zimber
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  2. Shlomo Ben-Efraim
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  3. David M. Weiss
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Additional information

Supported by Contract NO1-CM-12127 from the NCI and by research grants from Concern Foundation, Inc., the Lautenberg Endowment, the National Council for Research and Development, Israel, and the GSF Munich, Germany, and the Leukemia Research Foundation, Inc.

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Zimber, C., Ben-Efraim, S. & Weiss, D.M. Prevention by the MER tubercle bacillus fraction of immunosuppression induced by cancer chemotherapeutic agents. Cancer Immunol Immunother 3, 35–42 (1977). https://doi.org/10.1007/BF00199323

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  • DOI: https://doi.org/10.1007/BF00199323

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