Immunotherapeutic applications of radiation

Whole-body irradiation has been used with increasing success for nearly two decades to ablate neoplastic cells in the bone marrow. It is followed by allogeneic bone marrow transplant or a purged autologous graft to restore normal hematopoiesis. Total lymphoid irradiation (TLI), with sparing of the bone marrow, a procedure developed a decade ago, has been used as a treatment of Hodgkin's disease and autoimmune rheumatoid arthritis, and is now being tested in multiple sclerosis patients. With this treatment, patients receive 20 Gy (2000 rad) delivered in doses of 1.5-2 Gy (150-200 rad) per fraction for 2-3 weeks, to their cervical, axillary, mediastinal and hilar lymph nodes and the thymus. The patients are immunosuppressed and show long-lasting remissions in disease activity. Several months after TLI patients show a marked decrease in the percentage of total T cells and CD4+ cells, decreased mixed lymphocyte reaction (MLR) and decreased lymphocyte proliferation to T cell mitogens which is correlated with an increased ratio of CD8+ to CD4+ lymphocytes. Despite such marked immunosuppression, these patients do not experience any increase in the incidence of bacterial infections. In addition, allogeneic transplant survival was recently shown to be enhanced following TLI due to the T cell-mediated, acquired tolerance. Thus, radiation may be considered as a means of promoting tolerance to grafts prior to transplantation.

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