Radiation-Induced Augmentation of the Immune Response

  • Robert E. Anderson
  • Gary M. Troup
  • Ivan Lefkovits
Part of the Contemporary Topics in Immunobiology book series (CTI, volume 11)


The immunosuppressive effects of ionizing radiation were recognized early in the history of radiobiology. More recently, the differential radiosensitivity of the various components of the immune response has been documented (Anderson and Warner, 1976). Depending particularly upon the dose of radiation and the time between exposure and the introduction of antigen, irradiation may also augment primary and secondary immune responses (W. H. Taliaferro and L. G. Taliaferro, 1970; Dixon and McConahey, 1963). The latter phenomenon has not been studied nearly as extensively as the immunosuppressive effects, but sufficient data have been generated to prompt the advancement of several hypotheses to explain radiation-induced augmentation of immune responses. Of these, the two which have engendered most interest may be summarized as follows. (1) Dixon and colleagues (Dixon and McConahey, 1963; Schmidtke and Dixon, 1973; Hoffsten and Dixon, 1974) have suggested that the cellular proliferation after irradiation plus antigenic stimulation is more pronounced than after either stimulus alone. They further hypothesize that, following whole-body exposure, lymphoid tissues are repopulated disproportionately by rapidly dividing, antigen-stimulated lymphocytes. Thus, during the exaggerated proliferation induced by antigen plus radiation, the rapidly dividing, antigen-stimulated cells outstrip their nonstimulated counterparts resulting in augmented antibody production. (2) W. H. Taliaferro and co-workers (Taliaferro, 1957; W. H. Taliaferro and L. G. Taliaferro, 1950, 1951, 1954, 1957, 1964, 1969, 1970; Taliaferro et al.,1952, 1964), in reviewing their extensive experience on the immune consequences of radiation injury in rabbits, postulate that the release of nucleic acid degradation products stimulates particularly unprimed antibody-forming precursor cells which then recover more quickly than other lymphocytes and thus function in an exaggerated fashion.


Spleen Cell Thymus Cell Peak Titer Augmented Response Antigen Injection 
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  1. Anderson, R. E., and Warner, N. L., 1976, Ionizing radiation and the immune response, Ad v. Immunol 24: 215–335.CrossRefGoogle Scholar
  2. Anderson, R. E., and Williams, W. L., 1977, Radiosensitivity of T and B lymphocytes. V. Effects of whole-body irradiation on numbers of recirculating T cells and sensitization to primary skin grafts in mice, Am. J. Pathol 89: 367.PubMedGoogle Scholar
  3. Anderson, R. E., Standefer, J. C., and Scaletti, J. V., 1977, Radiosensitivity of defined populations of lymphocytes. VI. Functional, structural, and biochemical consequences of in vitro irradiation, Cell. Immunol 33: 45.PubMedCrossRefGoogle Scholar
  4. Angevine, M. D., and Tuggle, A., 1941, The effect of roentgen therapy upon infections produced in the skin of rabbits with cultures by Streptococcus haemolyticus and Staphylococcus aureus, Am. J. Roentgenol. and Radium Ther 46: 96.Google Scholar
  5. Benacerraf, B., Kapp, J. A., Debré, P., Pierce, C. W., and de la Croix, F., 1975, The stimulation of specific suppressor T cells in genetic non-responder mice by linear random copolymers of L-amino acids, Transplant. Rev 26: 21.PubMedGoogle Scholar
  6. Bensted, J. P. M., 1961, Haemagglutinin production in preimmunized mice exposed to continuous y-radiation, Nature (London) 190: 99.CrossRefGoogle Scholar
  7. Berenbaum, M. C., 1966, Radiosensitivity of immunologically activated cells, Nature (London) 209: 1313.CrossRefGoogle Scholar
  8. Chiorazzi, N., Fox, D. A., and Katz, D. H., 1976, Hapten-specific IgE antibody responses in mice. VI. Selective enhancement of IgE antibody production by low doses of x-irradiation and by cyclophosphamide, J. Immunol 117: 1629.PubMedGoogle Scholar
  9. Craddock, C. G., Jr., and Lawrence, J. S., 1948, The effect of roentgen irradiation on antibody formation in rabbits, J. Immunol 60: 241.PubMedGoogle Scholar
  10. Dean, D. M., Pross, H. F., and Kennedy, J. C., 1978. Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. III. Stimulatory and inhibitory effects of ionizing radiation, Int. J. Rad. Onc. Biol. Phys 4: 663.CrossRefGoogle Scholar
  11. DeMacedo, M. S., and Catty, D., 1977, Effect of x-irradiation on homocytotropic and agglutinating antibody production in mice, Immunology 33: 611.Google Scholar
  12. Dixon, F. J., and McConahey, P. J., 1963, Enhancement of antibody formation by whole body x-radiation, J. Exp. Med 117: 833.PubMedCrossRefGoogle Scholar
  13. Dutton, R. W., 1973, Inhibitory and stimulatory effects of concanavalin A on the response of mouse spleen cell suspensions to antigen. II. Evidence for separate stimulatory and inhibitory cells, J. Exp. Med 138: 1496.PubMedCrossRefGoogle Scholar
  14. Eardley, D. D., and Gershon, R. K., 1976, Induction of specific suppressor T cells in vitro, J. Immunol 117: 313.PubMedGoogle Scholar
  15. Eltringham, J. R., and Weissman, I. L., 1971, Differential effects of local lymphoid irradiation on delayed hypersensitivity and the serum antibody response in rats: Antigen injection before x-rays, J. Immunol 106: 1185.PubMedGoogle Scholar
  16. Fauci, A. S., Pratt, K. R., and Whalen, G., 1978, Activation of human lymphocytes. VIII. Differential radiosensitivity of subpopulations of lymphoid cells involved in the polyclonally-induced PFC responses of peripheral blood B lymphocytes, Immunology 35: 715.PubMedGoogle Scholar
  17. Fitch, F. W., Wissler, R. W., LaVia, M., and Barker, P., 1956, The timing of antigen injection relative to whole body x-irradiation and the development of circulating antibody and the splenic histologic reaction in the rat, J. Immunol 76: 151.PubMedGoogle Scholar
  18. Fox, D. A., Chiorazzi, N., and Katz, D. H., 1976, Hapten specific IgE antibody responses in mice. V. Differential resistance of IgE and IgG B lymphocytes to x-irradiation, J. Immunol 117: 1622.PubMedGoogle Scholar
  19. Gengozian, N., and Makinodan, T., 1958, Relation of primary antigen injection to time of irradiation on antibody production in mice, J. Immunol 80: 189.PubMedGoogle Scholar
  20. Graham, J.B., Graham, R. M., Neri, L., and Wright, K. A., 1956, Enhanced production of antibodies by local irradiation. I. Measurement of circulating antibodies, J. Immuno 76: 103.PubMedGoogle Scholar
  21. Hale, W. M., and Stoner, R. D., 1956, The effect of Cobalt-60 gamma radiation on tetanus antitoxin formation in mice, J. Immunol 77: 410.PubMedGoogle Scholar
  22. Hellström, K. E., Hellström, I., Kant, J. A., and Tamerius, J. D., 1978, Regression and inhibition of sarcoma growth by interference with a radiosensitive T-cell population, J. Exp. Med 148: 799.PubMedCrossRefGoogle Scholar
  23. Hirst, J. A., and Dutton, R. W., 1970, Cell components in the immune response. III. Neonatal thymectomy: Restoration in culture, Cell Immunol. 1: 190.PubMedCrossRefGoogle Scholar
  24. Hochman, P. S., Cudkowicz, G., and Dausset, J., 1978, Decline of natural killer cell activity in sublethally irradiated mice, J. Natl. Cancer Inst 61: 265.PubMedGoogle Scholar
  25. Hoffsten, P. E., and Dixon, F. J., 1974, Effect of irradiation and cyclophosphamide on antiKLH antibody formation in mice, J. Immunol 112: 564.PubMedGoogle Scholar
  26. Keightley, R. G., Cooper, M. D., and Lawton, A. R., 1976, The T dependence of B cell differentiation induced by pokeweed mitogen, J. Immunol 117: 1538.PubMedGoogle Scholar
  27. Kelly, J. F., and Dowell, D. A., 1941, Twelve-year review of x-ray therapy of gas gangrene, Radiology 37: 421.Google Scholar
  28. Kohn, H. I., 1951, Effect of x-rays upon hemolysin production in the rat, J. Immunol 66: 525.PubMedGoogle Scholar
  29. Lawrence, D. A., Eastman, A., Weigle, W. D., 1978, Murine T-cell preparations: Radiosensitivity of helper activity, Cell. Immunol 36: 97.PubMedCrossRefGoogle Scholar
  30. McCullagh, P., 1975, Radiosensitivity of suppressor cells in newborn rats, Aust. J. Exp. Biol. Med. Sci 53: 399.CrossRefGoogle Scholar
  31. Moretta, L., Webb, S. R., Grossi, C. E., Lydyard, P. M., and Cooper, M. D., 1977, Functional analysis of two human T-cell subpopulations. Help and suppression of B-cell responses by T cells bearing receptors for IgM or IgG, J. Exp. Med 146: 184.PubMedCrossRefGoogle Scholar
  32. Morgan, P., Sherwood, N. P., Werder, A. A., and Youngstrom, K., 1960, Studies on anaphylactic shock in the mouse. III. Effects of a single whole-body x-irradiation of 500 roentgens, J. Immunol 84: 325.PubMedGoogle Scholar
  33. Nichols, W. S., Troup, G. M., and Anderson, R. E., 1975, Radiosensitivity of sensitized and nonsensitized human lymphocytes evaluated in vitro, Am. J. Pathol 79: 499.PubMedGoogle Scholar
  34. Okumura, K., and Tada, T., 1971a, Regulation of homocytotropic antibody formation in the rat. III. Effect of thymectomy and splenectomy, J. Immunol 106: 1019.PubMedGoogle Scholar
  35. Okumura, K., and Tada, T., 1971b, Regulation of homocytotropic antibody formation in the rat. VI. Inhibitory effect of thymocytes on the homocytotropic antibody response, J. Immunol 107: 1682.PubMedGoogle Scholar
  36. Pfahler, G. E., 1943, The roentgen-ray treatment of acute inflammatory conditions, P. Med. J 47: 225.Google Scholar
  37. Rotter, V., and Trainin, N., 1975, Inhibition of tumor growth in syngeneic chimeric mice mediated by a depletion of suppressor T cells, Transplantation 20: 68.PubMedCrossRefGoogle Scholar
  38. Sabbadini, E., 1974, Regulation of cell-mediated cytotoxicity. I. Augmentation of cell-mediated cytotoxicity induced by radiation, J. Exp. Med 140: 470.PubMedCrossRefGoogle Scholar
  39. Schmidtke, J. R., and Dixon, F. J., 1973, Effects of sublethal irradiation on the plaque-forming cell response in mice, J. Immunol 111: 691.PubMedGoogle Scholar
  40. Siegal, F., and Siegal, M., 1977, Enhancement by irradiated T cells of human plasma cell production. Dissection of helper and suppressor functions in vitro, J. Immunol 118: 642.PubMedGoogle Scholar
  41. Silverman, M. S., and Chin, P. H., 1954, Quantitative serological determination of antibody formation in x-irradiated rabbits, J. Immunol 73: 120.PubMedGoogle Scholar
  42. Silverman, M. S., and Chin, P. H., 1956, The effect of whole body x-irradiation of mice on immunity to tetanus toxoid. II. The delayed immune response to injections of tetanus toxoid, J. Immunol 77: 266.PubMedGoogle Scholar
  43. Tada, T., Taniguchi, M., and Okumura, K., 1971, Regulation of homocytotropic antibody formation in the rat. II. Effect of x-irradiation, J. Immunol 106: 1012.PubMedGoogle Scholar
  44. Taliaferro, W. H., 1957, Modification of the immune response by radiation and cortisone, Ann. N.Y. Acad. Sci 69: 745.PubMedCrossRefGoogle Scholar
  45. Taliaferro, W. H., and Taliaferro, L. G., 1950, Effect of x-irradiation on hemolysin decline, J. Infect. Dis 87: 201.PubMedCrossRefGoogle Scholar
  46. Taliaferro, W. H., and Taliaferro, L. G., 1951, Effects of x-rays on immunity: A review, J. Immunol 66: 181.PubMedGoogle Scholar
  47. Taliaferro, W. H., and Taliaferro, L. G., 1954, Further studies on the radiosensitive stages in hemolysin formation, J. Infect. Dis 95: 134.PubMedCrossRefGoogle Scholar
  48. Taliaferro, W. H., and Taliaferro, L. G., 1957, The effect of repeated doses of x-rays on the hemolysin response in rabbits, J. Infect. Dis 101: 85.PubMedCrossRefGoogle Scholar
  49. Taliaferro, W. H., and Taliaferro, L. G., 1964, The relation of radiation dosage to enhancement, depression, and recovery of the initial Forssman hemolysin response in rabbits, J. Infect. Dis 114: 285.PubMedCrossRefGoogle Scholar
  50. Taliaferro, W. H., and Taliaferro, L. G., 1969, Effects of radiation on the initial and anamnestic responses in rabbits: Antigen injection after x-rays, J. Immunol 103: 559.PubMedGoogle Scholar
  51. Taliaferro, W. H., and Taliaferro, L. G., 1970, Effects of irradiation on initial and anamnestic hemolysin responses in rabbits: Antigen injection before x-rays, J. Immunol 104: 1364.PubMedGoogle Scholar
  52. Taliaferro, W. H., Taliaferro, L. G., and Janssen, E. F., 1952, The localization of x-ray injury to the initial phases of antibody response, J. Infect. Dis 91: 105.PubMedCrossRefGoogle Scholar
  53. Taliaferro, W. H., Taliaferro, L. G., and Jaroslow, B. N., 1964, Radiation and the Immune Mechanism, Academic Press, New York.Google Scholar
  54. Troup, G. M., Anderson, R. E., Pogue, L., and Baker, B., 1979, Augmentation of mixed leukocyte reactions by low-dose irradiation (abstract), Fed. Proc 38: 1173.Google Scholar
  55. Tse, H. Y., and Dutton, R. W., 1977, Separation of helper and suppressor T lymphocytes. II. Ly phenotypes and lack of DNA synthesis requirement for the generation of concanavalin A helper and suppressor cells, J. Exp. Med 146: 747.PubMedCrossRefGoogle Scholar
  56. van der Gaag, R., and McCullagh, P., 1975, Facilitation of the growth of an allogeneic tumor by suppressor cells in newborn rats, Aust. J. Exp. Biol. Med. Sci 53: 421.CrossRefGoogle Scholar
  57. Warner, N. L., and Anderson, R. E., 1975, Helper effect of normal and irradiated thymus cells on transferred immunoglobulin production, Nature (London) 254: 604.CrossRefGoogle Scholar
  58. Zatz, M. M., and Gershon, R. K., 1975, Regulation of lymphocyte trapping: The negative trap, J. Immunol 115: 450PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • Robert E. Anderson
    • 1
  • Gary M. Troup
    • 1
  • Ivan Lefkovits
    • 2
  1. 1.Department of PathologyUniversity of New Mexico School of MedicineAlbuquerqueUSA
  2. 2.Basel Institute for ImmunologyBaselSwitzerland

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