Prevention of graft rejection in allogeneic bone marrow transplantation. II. Preclinical studies with three radiation protocols.
Three radiotherapeutic regimens were compared in vitro to determine their immunosuppressive potential against non-MHC-restricted cytotoxic cells. Assays of natural killer and lymphokine-activated killer function, and cytotoxicity against allogeneic cells were used to quantitate the cytotoxic potential of peripheral blood mononuclear cells from healthy individuals following irradiation with a single dose of 1000 cGy on day 0, 1320 cGy of fractionated radiation (165 cGy b.i.d. x 4 days), or "split-dose" irradiation consisting of 1000 cGy on day 0 followed 5 or 7 days later by 500 cGy. Both irradiated and nonirradiated (control) PBMC cultures were maintained in culture with medium containing interleukin-2, immunophenotyped, and assayed for cytotoxicity from 1 to 8 days after irradiation. Single dose and fractionated-dose irradiation resulted in a progressive decline in cytotoxic capacity, with an 80% inhibition of both NK and LAK cell activity 8 days after onset of irradiation. The split dose of 500 cGy administered 7 days after a dose of 1000 cGy was found to be the most effective in eliminating NK (93% inhibition) and LAK (100% inhibition) cytotoxicity. These data indicate that split-dose irradiation may result in greater immuno-suppression than single-dose or fractionated irradiation.
Department of Pediatrics, University of Minnesota, Minneapolis 55455.
G P
GP
Malilay
E A
EA
Sevenich
A H
AH
Filipovich
D016026:Bone Marrow Transplantation / Q000276:immunology; D002588:Cesium Radioisotopes; D003602:Cytotoxicity, Immunologic / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006084:Graft Rejection / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology / Q000528:radiation effects; D007694:Killer Cells, Natural / Q000276:immunology / Q000528:radiation effects; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000528:radiation effects*; D008212:Lymphocyte Depletion; D010641:Phenotype; D011183:Postoperative Complications / Q000517:prevention & control; D013601:T-Lymphocytes / Q000166:cytology
D002588:Cesium Radioisotopes; D007376:Interleukin-2