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. 1987 Nov;84(22):8080–8084. doi: 10.1073/pnas.84.22.8080

Low-temperature culture of human islets or in vivo treatment with L3T4 antibody produces a marked prolongation of islet human-to-mouse xenograft survival.

C Ricordi 1, P E Lacy 1, K Sterbenz 1, J M Davie 1
PMCID: PMC299481  PMID: 3120184

Abstract

In previous studies we have shown that rejection of islet xenografts transplanted between closely related species (rat to mouse) can be prevented by destruction or alteration of antigen-presenting cells in the donor islets and temporary immunosuppression of the recipients. Relatively few studies have been reported on the survival of islet xenografts transplanted between widely discordant species. In the present study, isolated human islets were transplanted beneath the renal capsule of B6 mice made diabetic by the injection of streptozotocin. The effect of culturing the human islets at 24 degrees C for 7 days with or without the administration of anti-L3T4 for 7 days after transplantation was determined. A marked prolongation of the mean survival time was obtained with low-temperature culture alone (greater than 40.2 +/- 9.9 days), with anti-L3T4 alone (greater than 45.2 +/- 6.3 days), and with the combination of these regimens (greater than 51.9 +/- 5.1 days) as compared to controls (7.5 +/- 1.1 days). The surprising finding was the marked effect of low-temperature culture alone on prolonging human islet xenograft survival because this treatment of the donor islets had no effect on the survival of rat islet xenografts. Intact human islets were present in approximately equal to 80% of the recipients after returning to a diabetic state, whereas xenografts of rat islets were completely destroyed. The findings indicate that complete rejection of islets across this widely discordant species barrier is slower than across a closely related barrier and may be occurring by a different rejection process.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bowen K. M., Lafferty K. J. Reversal of diabetes by allogenic islet transplantation without immunosuppression. Aust J Exp Biol Med Sci. 1980 Oct;58(5):441–447. doi: 10.1038/icb.1980.45. [DOI] [PubMed] [Google Scholar]
  2. Chabot J., Weber C., Hardy M. A., Rivera S., Bailey-Braxton D., Strausberg L., Wood M., Chow J., Pi-Sunyer F. X., Reemtsma K. Synergy of ALS and UV-B in prolongation of primate-to-mouse islet xenograft survival. Transplant Proc. 1987 Feb;19(1 Pt 2):1160–1165. [PubMed] [Google Scholar]
  3. Deodhar S. D. Review of xenografts in organ transplantation. Transplant Proc. 1986 Jun;18(3 Suppl 2):83–87. [PubMed] [Google Scholar]
  4. Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
  5. Eloy R., Haffen K., Kedinger M., Grenier J. F. Chick embryo pancreatic transplants reverse experimental diabetes of rats. J Clin Invest. 1979 Aug;64(2):361–373. doi: 10.1172/JCI109470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Faustman D. L., Steinman R. M., Gebel H. M., Hauptfeld V., Davie J. M., Lacy P. E. Prevention of rejection of murine islet allografts by pretreatment with anti-dendritic cell antibody. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3864–3868. doi: 10.1073/pnas.81.12.3864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Faustman D., Hauptfeld V., Lacy P., Davie J. Prolongation of murine islet allograft survival by pretreatment of islets with antibody directed to Ia determinants. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5156–5159. doi: 10.1073/pnas.78.8.5156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gutstein N. L., Seaman W. E., Scott J. H., Wofsy D. Induction of immune tolerance by administration of monoclonal antibody to L3T4. J Immunol. 1986 Aug 15;137(4):1127–1132. [PubMed] [Google Scholar]
  9. Lacy P. E., Davie J. M., Finke E. H. Induction of rejection of successful allografts of rat islets by donor peritoneal exudate cells. Transplantation. 1979 Nov;28(5):415–420. doi: 10.1097/00007890-197911000-00014. [DOI] [PubMed] [Google Scholar]
  10. Lacy P. E., Davie J. M., Finke E. H. Prolongation of islet allograft survival following in vitro culture (24 degrees C) and a single injection of ALS. Science. 1979 Apr 20;204(4390):312–313. doi: 10.1126/science.107588. [DOI] [PubMed] [Google Scholar]
  11. Lacy P. E., Davie J. M., Finke E. H. Prolongation of islet xenograft survival without continuous immunosuppression. Science. 1980 Jul 11;209(4453):283–285. doi: 10.1126/science.6770465. [DOI] [PubMed] [Google Scholar]
  12. Lacy P. E., Davie J. M. Transplantation of pancreatic islets. Annu Rev Immunol. 1984;2:183–198. doi: 10.1146/annurev.iy.02.040184.001151. [DOI] [PubMed] [Google Scholar]
  13. Lacy P. E., Kostianovsky M. Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes. 1967 Jan;16(1):35–39. doi: 10.2337/diab.16.1.35. [DOI] [PubMed] [Google Scholar]
  14. Lacy P. E., Walker M. M., Fink C. J. Perifusion of isolated rat islets in vitro. Participation of the microtubular system in the biphasic release of insulin. Diabetes. 1972 Oct;21(10):987–998. doi: 10.2337/diab.21.10.987. [DOI] [PubMed] [Google Scholar]
  15. Lau H., Reemtsma K., Hardy M. A. Prolongation of rat islet allograft survival by direct ultraviolet irradiation of the graft. Science. 1984 Feb 10;223(4636):607–609. doi: 10.1126/science.6420888. [DOI] [PubMed] [Google Scholar]
  16. Lindall A., Steffes M., Sorenson R. Immunoassayable insulin content of subcellular fractions of rat islets. Endocrinology. 1969 Aug;85(2):218–223. doi: 10.1210/endo-85-2-218. [DOI] [PubMed] [Google Scholar]
  17. Miller S. D., Jenkins M. K. In vivo effects of GK1.5 (anti-L3T4a) monoclonal antibody on induction and expression of delayed-type hypersensitivity. Cell Immunol. 1985 May;92(2):414–426. doi: 10.1016/0008-8749(85)90022-x. [DOI] [PubMed] [Google Scholar]
  18. Perper R. J., Najarian J. S. Experimental renal heterotransplantation. I. In widely divergent species. Transplantation. 1966 Jul;4(4):377–388. doi: 10.1097/00007890-196607000-00002. [DOI] [PubMed] [Google Scholar]
  19. Shizuru J. A., Gregory A. K., Chao C. T., Fathman C. G. Islet allograft survival after a single course of treatment of recipient with antibody to L3T4. Science. 1987 Jul 17;237(4812):278–280. doi: 10.1126/science.2955518. [DOI] [PubMed] [Google Scholar]
  20. Weber C., Weil R., 3rd, McIntosh R., Hogle H., Warden G., Reemtsma K. Xenotransplantation of piscine islets into hyperglycemic rats. Surgery. 1975 Feb;77(2):208–215. [PubMed] [Google Scholar]
  21. Wofsy D., Mayes D. C., Woodcock J., Seaman W. E. Inhibition of humoral immunity in vivo by monoclonal antibody to L3T4: studies with soluble antigens in intact mice. J Immunol. 1985 Sep;135(3):1698–1701. [PubMed] [Google Scholar]

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