Abstract
Total lymphoid irradiation (TLI) is immunosuppressive and, in rodent, can induce a state where transplantation of allogeneic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. We attempted to apply this treatment to a large animal model. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950-3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned (serum creatinine level less than 2.0 mg/dl) for a mean +/- (SE) of 4.7 +/- 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15-76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemagglutinin and in mixed lymphocyte culture was suppressed for at least on month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bach M. L., Bach F. H., Rasmus W., Burkholder P. M., Dufek J., Kahn D. DL-A LD matching: its prognostic value for kidney allograft survival. Transplant Proc. 1975 Sep;7(3):423–425. [PubMed] [Google Scholar]
- Bieber C. P., Jamieson S., Raney A., Burton N., Bogarty S., Hoppe R., Kaplan H. S., Strober S., Stinson E. B. Cardiac allograft survival in rhesus primates treated with combined total lymphoid irradiation and rabbit antithymocyte globulin. Transplantation. 1979 Oct;28(4):347–350. doi: 10.1097/00007890-197910000-00017. [DOI] [PubMed] [Google Scholar]
- Slavin S., Fuks Z., Kaplan H. S., Strober S. Transplantation of allogeneic bone marrow without graft-versus-host disease using total lymphoid irradiation. J Exp Med. 1978 Apr 1;147(4):963–972. doi: 10.1084/jem.147.4.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Slavin S., Gottlieb M., Strober S., Bieber C., Hoppe R., Kaplan H. S., Grumet F. C. Transplantation of bone marrow in outbred dogs without graft-versus-host disease using total lymphoid irradiation. Transplantation. 1979 Feb;27(2):139–142. [PubMed] [Google Scholar]
- Slavin S., Reitz B., Bieber C. P., Kaplan H. S., Strober S. Transplantation tolerance in adult rats using total lymphoid irradiation: permanent survival of skin, heart, and marrow allografts. J Exp Med. 1978 Mar 1;147(3):700–707. doi: 10.1084/jem.147.3.700. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Slavin S., Strober S., Fuks Z., Kaplan H. S. 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. 1977 Jul 1;146(1):34–48. doi: 10.1084/jem.146.1.34. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Slavin S., Strober S., Fuks Z., Kaplan H. S. Long-term survival of skin allografts in mice treated with fractionated total lymphoid irradiation. Science. 1976 Sep 24;193(4259):1252–1254. doi: 10.1126/science.785599. [DOI] [PubMed] [Google Scholar]
- Slavin S., Zan-Bar I., Strober S. Generation of protein-specific and alloantigen-specific suppressor cells following total lymphoid irradiation in mice. Transplant Proc. 1979 Mar;11(1):891–894. [PubMed] [Google Scholar]
- Sutherland D. E., Lum C. T., Payne W. D., Najarian J. S. Effect of pretreatment with donor blood on renal allograft survival in dogs stratified by DLA match and MLC reactivity. Transplant Proc. 1979 Mar;11(1):160–166. [PubMed] [Google Scholar]