In vitro allograft irradiation prevents graft-versus-host disease in small-bowel transplantation.
In small-bowel transplantation, the transfer of large numbers of donor lymphocytes with the intestinal allograft may provoke a lethal graft-versus-host reaction. The effectiveness of allograft irradiation in vitro as a method of preventing graft-versus-host disease (GVHD) was studied in a rat model of small-bowel transplantation, with the Lewis----Lewis X Brown Norway F1 hybrid strain combination. Cold harvested small-bowel allografts were irradiated immediately prior to heterotopic or orthotopic transplantation. Animals that had received heterotopic allografts irradiated with 0, 250, or 500 rad all died of GVHD after 14.4 +/- 3.0, 15.0 +/- 1.3, and 14.2 +/- 1.9 days, respectively. None of the animals that had received allografts treated with 1000 rad developed clinical or pathologic evidence of GVHD, however, and all survived for more than 6 months (P less than 0.001). Allograft function was studied in animals that underwent orthotopic transplantation. Recipients of nonirradiated orthotopic allografts all died of GVHD after 14.0 +/- 0.7 days, whereas recipients of allografts irradiated with 1000 rad all survived for more than 5 months (P less than 0.001). After 120 days, weight gain (51.8 +/- 11.7%), serum albumin (3.9 +/- 0.7 g/dl), serum triglycerides (67.0 +/- 24.3 mg/dl), CBC, and differential in these animals were not statistically different from those in either age-matched isograft recipients or normal animals, and when the rats were sacrificed, irradiated allografts showed no changes suggestive of radiation injury. These results indicate that irradiation of small-bowel allografts in vitro prevents development of GVHD, and that this can be achieved at a dose which does not cause injury to or malfunction of the allograft.
D000818:Animals; D001835:Body Weight; D006086:Graft vs Host Disease / Q000473:pathology / Q000517:prevention & control*; D006087:Graft vs Host Reaction; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000473:pathology / Q000528:radiation effects / Q000637:transplantation*; D008198:Lymph Nodes / Q000528:radiation effects*; D008212:Lymphocyte Depletion; D008297:Male; D011829:Radiation Dosage; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000032:analysis; D013154:Spleen / Q000166:cytology; D014280:Triglycerides / Q000097:blood
D012709:Serum Albumin; D014280:Triglycerides