Total Lymphoid Irradiation

  • Brian L. Kotzin
  • Samuel Strober

Abstract

There remains a great need in medicine for new immunosuppressive therapies that are capable of suppressing disease activity but are not associated with the complications of general cytotoxicity and nonselective immunosuppression. Currently available immunosuppressive drugs are too frequently associated with serious and sometimes lethal complications. We review here the relatively unique immunologic changes associated with total lymphoid irradiation (TLI) and the development of this form of radiotherapy as an immunosuppressive treatment for rheumatic diseases.

Keywords

Arthritis Flare Neutropenia Cyclosporin Thrombocytopenia 

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References

  1. Andrews, B. S., Eisenberg, R. A., Theofilipoulous, A. N., Izui, S., Wilson, C. B., McConahey, P. J., Murphy, E. D., Roths, J. B., and Dixon, F. J., 1978, Spontaneous murine lupus-like syndromes: Clinical and immunopathological manifestations in several strains,J. Exp. Med.148: 1198–1215.PubMedCrossRefGoogle Scholar
  2. Baccarini, M., Bosi, A., and Papa, G., 1980, Second malignancy in patients treated for Hodgkin’s disease,Cancer46: 1735–1740.CrossRefGoogle Scholar
  3. Coleman, C. N., Williams, C. J., Flint, A., Glatstein, E., Rosenberg, S. A., and Kaplan, H. S., 1977, Hematologic neoplasia in patients treated for Hodgkin’s disease,N. Engl. J. Med.297: 1249–1252.PubMedCrossRefGoogle Scholar
  4. Fauci, A. S., Whalen, G., and Burch, C, 1980, Activation of human B lymphocytes. XVI. Cellular requirements, interactions, and immunoregulation of pokeweed mitogen-induced total-immunoglobulin producing plaque-forming cells in peripheral blood,Cell. Immunol.54: 230–240.PubMedCrossRefGoogle Scholar
  5. Field, E. H., Strober, S., Hoppe, R. T., Calin, A., Engleman, E. G., Kotzin, B. L., Tanay, A. S., Calin, H. J., Terrell, C. P., and Kaplan, H. S., 1983, Sustained improvement of intractable rheumatoid arthritis after total lymphoid irradiation,Arthritis Rheum. 26: 937–946.PubMedCrossRefGoogle Scholar
  6. Field, E. H., Engleman, E. G., Terrell, C. P., and Strober, S., 1984a, Reduced in vitro immune responses of purified human Leu-3 (helper/inducer phenotype) cells after total lymphoid irradiation.J. Immunol.132: 1031–1035.PubMedGoogle Scholar
  7. Fuks, Z., Strober, S., Bobrove, A. M., Sasazuki, T., McMichael, A., and Kaplan, H. S., 1976, Long-term effects of radiation on T and B lymphocytes in peripheral blood of patients with Hodgkin’s disease, J. Clin. Invest. 58: 803–814.PubMedCrossRefGoogle Scholar
  8. Gottlieb, M., Strober, S., Hoppe, R. T., Grumet, F. C., and Kaplan, H. S., 1980, Engraftment of allogeneic bone marrow without graft-versus-host disease in mongrel dogs using total lymphoid irradiation,Transplantation29: 487–491.PubMedGoogle Scholar
  9. Gottlieb, M., Strober, S., and Kaplan, H. S., 1981, Cellular basis of graft versus host tolerance in chimeras prepared with total lymphoid irradiation (TLI),J. Exp. Med.152: 736–741.CrossRefGoogle Scholar
  10. Helfgott, S., Brahn, E., Trentham, D., Belli, J., Anderson, R., Reinherz, E., Schlossman, S., and Austin, K. F., 1983, Long-term effects of total lymphoid irradiation in refractory rheumatoid arthritis,Arthritis Rheum. 26: S7.Google Scholar
  11. Hess, A. D., and Tutschka, P. J., 1980, Effect of cyclosporin A on human lymphocyte responses in vitrol 1. Cs A allows for the expression of alloantigen-activated suppressor cells while preferentially inhibiting the induction of cytolytic effector lymphocytes in MLR,J. Immunol.124: 2601–2608.PubMedGoogle Scholar
  12. Howie, J. B., andHelyer, B. J., 1968, The immunology and pathology of NZB mice,Adv. Immunol.9: 215–284.PubMedCrossRefGoogle Scholar
  13. Kaplan, H. S., 1980,Hodgkin’s Disease, ed. 2, Harvard University Press, Cambridge, Massachusetts.Google Scholar
  14. Keightley, R. G., Cooper, M. D., and Lawton, A. R., 1976, The T cell dependence of B cell differentiation induced by pokeweed mitogen,J. Immunol.117: 1538–1544.PubMedGoogle Scholar
  15. King, D. P., Strober, S., and Kaplan, H. S., 1981, Suppression of the mixed leukocyte response and of graft- versus-host disease by spleen cells following total lymphoid irradiation (TLI),J. Immunol.126: 1140–1145.PubMedGoogle Scholar
  16. Kotzin, B. L., and Strober, S., 1979, Reveral of NZB/NZW disease with total lymphoid irradiation,J. Exp. Med.150: 371–378.PubMedCrossRefGoogle Scholar
  17. Kotzin, B. L., Strober, S., Engleman, E. G., Calin, A., Hoppe, R. T., Kansas, G. S., Terrell, C. P., and Kaplan, H. S., 1981, Treatment of intractable rheumatoid arthritis with total lymphoid irradiation,N. Engl. J. Med.305: 969–976.PubMedCrossRefGoogle Scholar
  18. Kotzin, B. L., Kansas, G. S., Engleman, E. G., Hoppe, R. T., Kaplan, H. S., and Strober, S., 1983a, Changes in T-cell subsets in patients with rheumatoid arthritis treated with total lymphoid irradiation,Clin. Immunol. Immunopathol.27: 250–260.PubMedCrossRefGoogle Scholar
  19. Kotzin, B. L., Ward, R., and Strober, S., 1983b, Failure of NZB/NZW spleen cells to re-establish disease in irradiated syngeneic recipients,Arthritis Rheum. 26: S75.Google Scholar
  20. Kotzin, B. L., Strober, S., Kansas, G. S., Terrell, C. P., and Engleman, E. G., 1984, Suppression of pokeweed mitogen stimulated immunoglobulin production in patients with rheumatoid arthritis after treatment with total lymphoid irradiation,J. Immunol.132: 1049–1055.PubMedGoogle Scholar
  21. Krikorian, J. G., Burke, J. S., Rosenberg, S. A., and Kaplan, H. S., 1979, Occurrence of non-Hodgkin’s lymphoma after therapy for Hodgkin’s disease,N. Engl. J. Med.300: 452–458.PubMedCrossRefGoogle Scholar
  22. Lowry, R. P., Forbes, R. D., and Blackburn, J. H., 1984a, Immune reactivity and immunosuppressive intervention (TLI) in experimental nephritis. 1. Immunopathologic correlates in the accelerated autologous form of nephrotoxic serum nephritis,J. Immunol.132: 1001–1006.PubMedGoogle Scholar
  23. Lowry, R. P., Forbes, R. D., Carpenter, C. B., Gurley, K. E., and Merrill, J. P., 1984b, Immune reactivity and immunosuppressive intervention in experimental nephritis. 11. Effect of TLI on the course of two models of nephritis in the inbred rat,J. Immunol.132: 1007–1012.PubMedGoogle Scholar
  24. May, R. D., Slavin, S., and Vitetta, E. S., 1983, The partial characterization of suppressor cells in the spleens of mice conditioned with fractionated total lymphoid irradiation (TLI),J. Immunol.131: 1108–1114.PubMedGoogle Scholar
  25. Neale, T. J., and Wilson, C. B., 1982, Glomerular antigens in Heymann’s nephritis: Reactivity of eluted and circulating antibody,J. Immunol.128: 323–330.PubMedGoogle Scholar
  26. Okada, S., and Strober, S., 1982, Spleen cells from adult mice given total lymphoid irradiation (TLI) or from newborn mice have similar regulatory effects in the mixed leukocyte reaction (MLR). 1. Generation of antigen-specific suppressor cells in the mixed leukocyte reaction after the addition of spleen cells from adult mice given total lymphoid irradiation,J. Exp. Med.156: 522–538.PubMedCrossRefGoogle Scholar
  27. Oseroff, A., Okada, S., and Strober, S., 1984, Natural suppressor (NS) cells found in the spleen of neonatal mice and of adult mice given total lymphoid irradiation (TLI) express the null surface phenotype,J. Immunol.132: 101–110.PubMedGoogle Scholar
  28. Prud’homme, G. J., Park, C. L., Feiser, T. M., Kofler, R., Dixon, F. J., and Theofilopoulos, A. N., 1983, Identification of a B cell differentiation factor(s) spontaneously produced by proliferating T cells in murine lupus strains of the lpr/lpr genotype,J. Exp. Med.157: 730–742.PubMedCrossRefGoogle Scholar
  29. Reinherz, E. L., Morimoto, C., Penta, A. C., and Schlossman, S. F., 1980, Regulation of B cell immunoglobulin secretion by functional subsets of T lymphocytes in man,Eur. J. Immunol.10: 570–572.PubMedCrossRefGoogle Scholar
  30. Rosenberg, S. A., and Lipsky, P. E., 1979, Monocyte dependence of pokeweed mitogen-induced differentiation of immunoglobulin-secreting cells from human peripheral blood mononuclear cells,J. Immunol.122: 926–931.PubMedGoogle Scholar
  31. Schurman, D. J., Hirshman, P., and Strober, S., 1981, Total lymphoid irradiation and local joint irradiation in the treatment of adjuvant arthritis,Arthritis Rheum. 24: 38–44.PubMedCrossRefGoogle Scholar
  32. Slavin, S., Strober, S., Fuks, Z., and Kaplan, H. S., 1976, Long-term survival of skin allografts in mice treated with fractionated total lymphoid irradiation,Science193: 1252–1255.PubMedCrossRefGoogle Scholar
  33. Slavin, S., Strober, S., Fuks, Z., and Kaplan, H. S., 1977, Induction of specific tissue transplantation tolerance using fractionated total lymphoid irradiation in adult mice: Long-term survival of allogeneic bone marrow and skin grafts,J. Exp. Med.146: 34–48.PubMedCrossRefGoogle Scholar
  34. Slavin, S., Reitz, B., Bieber, C. P., Kaplan, H. S., and Strober, S., 1978, Transplantation tolerance in adult rats using total lymphoid irradiation: Permanent survival of skin, heart and marrow allografts,J. Exp. Med.147: 700–707.PubMedCrossRefGoogle Scholar
  35. Strober, S., Tanay, A., Field, E., Hoppe, R. T., Calin, A., Engleman, E. G., Kotzin, B. L., Brown, B. W., and Kaplan, H. S., 1985a, Efficacy of total lymphoid irradiation in intractable rheumatoid arthritis: A double-blind randomized trial,Ann. Intern. Med.102: 441–449.PubMedGoogle Scholar
  36. Strober, S., Field, E., Hoppe, R. T., Kotzin, B. L., Shemesh, O., Engleman, E., Ross, J. C., and Meyers, B. D., 1985b, Treatment of intractable lupus nephritis with total lymphoid irradiation,Ann. Intern. Med.102: 450–458.PubMedGoogle Scholar
  37. Tanay, A., and Strober, S., 1984, Opposite effects of total lymphoid irradiation on T cell dependent and T cell independent antibody responses,J. Immunol.132: 979–984.PubMedGoogle Scholar
  38. Tanay, A., Strober, S., Logue, G. L., and Schiffman, G., 1984, Use of total lymphoid irradiation (TLI) in studies of the T cell dependence of autoantibody production in rheumatoid arthritis,J. Immunol.132: 1036–1040.PubMedGoogle Scholar
  39. Theofilopoulos, A. N., Balderas, R., Schawler, D. L., Izui, S., Kotzin, B. L., Strober, S., and Dixon, F. J., 1980, Inhibition of T cell proliferation and SLE-like syndrome of MRL/1 mice by whole body or total lymphoid irradiation,J. Immunol.125: 2137–2142.PubMedGoogle Scholar
  40. Trentham, D. E., Belli, J. A., Anderson, R. J., Buckley, J. A., Goetzl, E. J., David, J. R., and Austen, K. F., 1981, Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis,N. Engl. J. Med.305: 976–982.PubMedCrossRefGoogle Scholar
  41. Valagussa, P., Santoro, A., Kenda, R., Fossati Bellani, F., Franchi, F., Banfi, A., Rilke, F., and Bonadonna, G., 1980, Second malignancies in Hodgkin’s disease: A complication of certain forms of treatment,Br. Med. J.280: 216–219.PubMedCrossRefGoogle Scholar
  42. Zan-Bar, I., Slavin, S., and Strober, S., 1978, Induction and mechanism of tolerance to bovine serum albumin in mice given total lymphoid irradiation (TLI),J. Immunol.121: 1400–1404.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1985

Authors and Affiliations

  • Brian L. Kotzin
    • 1
    • 2
  • Samuel Strober
    • 3
  1. 1.Department of MedicineUniversity of Colorado Health Science CenterUSA
  2. 2.Rheumatology SectionVeteran Administration Medical CenterDenverUSA
  3. 3.Department of Medicine, Division of ImmunologyStanford University Medical CenterStanfordUSA

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