Prevention of cyclosporine-induced syngeneic graft-versus-host disease in bone marrow transplantation by UV-B irradiated bone marrow cells.
UV-B irradiation of allogeneic rat bone marrow cells (BMC) transplanted into lethally gamma-irradiated recipients prevents GVHD and induces stable complete hematopoietic chimerism. Cyclosporine (CsA), an effective immunosuppressive agent, causes an autoimmune syndrome termed syngeneic GVHD in syngeneic radiation chimeras following discontinuation of CsA. To understand the in vivo interactions of CsA with UV-B modulated syngeneic bone marrow transplant (BMT), as this is essential before clinical use, we studied the effects of CsA therapy in recipients of UV-B irradiated donor BMT in the rat model. Lethally irradiated (10.5 Gy) Lewis recipients of naive or UV-B irradiated syngeneic BMT (admixture of 10(8) BMC and 5 x 10(6) spleen cells) were treated with CsA (i.m. 12.5 mg/kg/day) for 30 consecutive days after BMT. The results show that all irradiated Lewis recipients of syngeneic BMT modulated with 700 J/m2 UV-B were hematologically fully reconstituted in 25-35 days and survived their normal life span. In contrast, all lethally irradiated recipients of untreated BMT that received CsA for 30 days developed lethal acute syngeneic GVHD 7-12 days after CsA withdrawal. Of interest is the finding that while higher doses of UV-B (500-700 J/m2) irradiation of BMC prior to transplantation into CsA-treated animals prevented hemopoietic reconstitution, lower doses (100-300 J/m2) allowed for hemopoietic recovery and, in addition, prevented the development of syngeneic GVHD following the discontinuation of CsA. The development of syngeneic GVHD was dependent on the presence of the thymus and did not occur in thymectomized recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
Ohajekwe
O A
OA
Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
James
T
T
Hardy
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MA
Oluwole
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SF
D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects*; D016026:Bone Marrow Transplantation; D016572:Cyclosporine / Q000009:adverse effects*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013934:Thymectomy; D014184:Transplantation, Homologous; D014466:Ultraviolet Rays
D016207:Cytokines; D016572:Cyclosporine