Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1995 Feb;84(2):333–336.

Migration of donor cells into the thymus is not essential for induction and maintenance of systemic tolerance after liver transplantation in the rat.

E Kobayashi 1, N Kamada 1, L Delriviere 1, R Lord 1, S Goto 1, N I Walker 1, S Enosawa 1, M Miyata 1
PMCID: PMC1415086  PMID: 7751012

Abstract

In this study, we show that cells encoded by donor-type major histocompatibility complex (MHC) class I antigens effectively migrate into the thymus of the host after liver transplantation. However, the thymus is not essential for the induction and maintenance of tolerance after orthotopic rat liver transplantation (OLT). Liver allografted rats in the DA(RT1a) into PVG (RT1c) combination survived without immunosuppressive agents. The thymus of the host showed a transitory atrophy and returned to normal weight 4 weeks after OLT. Donor antigens were detected in the host thymus after OLT. Adult PVG rats that had been thymectomized 1 week before implantation of DA liver grafts showed liver graft survival without immunosuppression. DA heart grafts were heterotopically transplanted into the PVG thymectomized, liver-grafted rats 1-4 weeks after OLT. No rejection of the cardiac allografts was observed. Systemic tolerance was induced and maintained in the absence of the thymus.

Full text

PDF
333

Images in this article

334Figure 2
on p.334
335Figure 3
on p.335
335Figure 4
on p.335

Selected References

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

  1. Agus D. B., Surh C. D., Sprent J. Reentry of T cells to the adult thymus is restricted to activated T cells. J Exp Med. 1991 May 1;173(5):1039–1046. doi: 10.1084/jem.173.5.1039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andrzejewski W., Chomiczewski K., Tchórzewski H. Morphology of thymus and lymph nodes after orthotopic and heterotopic liver transplantation in rat. Acta Med Pol. 1981;22(3):181–191. [PubMed] [Google Scholar]
  3. Besedovsky H. O., del Rey A., Sorkin E. Role of prethymic cells in acquisition of self-tolerance. J Exp Med. 1979 Dec 1;150(6):1351–1358. doi: 10.1084/jem.150.6.1351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bradley S. M., Morrissey P. J., Sharrow S. O., Singer A. Tolerance of thymocytes to allogeneic I region determinants encountered prethymically. Evidence for expression of anti-Ia receptors by T cell precursors before their entry into the thymus. J Exp Med. 1982 Jun 1;155(6):1638–1652. doi: 10.1084/jem.155.6.1638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Calne R. Y., Sells R. A., Pena J. R., Davis D. R., Millard P. R., Herbertson B. M., Binns R. M., Davies D. A. Induction of immunological tolerance by porcine liver allografts. Nature. 1969 Aug 2;223(5205):472–476. doi: 10.1038/223472a0. [DOI] [PubMed] [Google Scholar]
  6. Demetris A. J., Murase N., Starzl T. E. Donor dendritic cells after liver and heart allotransplantation under short-term immunosuppression. Lancet. 1992 Jun 27;339(8809):1610–1610. doi: 10.1016/0140-6736(92)91875-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Good R. A. Mixed chimerism and immunologic tolerance. N Engl J Med. 1993 Mar 18;328(11):801–802. doi: 10.1056/NEJM199303183281111. [DOI] [PubMed] [Google Scholar]
  8. Goss J. A., Nakafusa Y., Flye M. W. Intrathymic injection of donor alloantigens induces donor-specific vascularized allograft tolerance without immunosuppression. Ann Surg. 1992 Oct;216(4):409–416. doi: 10.1097/00000658-199210000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Howard J. C., Butcher G. W., Licence D. R., Galfrè G., Wright B., Milstein C. Isolation of six monoclonal alloantibodies against rat histocompatibility antigens: clonal competition. Immunology. 1980 Sep;41(1):131–141. [PMC free article] [PubMed] [Google Scholar]
  10. Kamada N., Calne R. Y. A surgical experience with five hundred thirty liver transplants in the rat. Surgery. 1983 Jan;93(1 Pt 1):64–69. [PubMed] [Google Scholar]
  11. Kamada N., Davies H. S., Roser B. Reversal of transplantation immunity by liver grafting. Nature. 1981 Aug 27;292(5826):840–842. doi: 10.1038/292840a0. [DOI] [PubMed] [Google Scholar]
  12. Kamada N., Kobayashi E., Delriviere L., Goto S., Lord R., Enosawa S., Saito T., Toyama N. Migration of cells encoded by donor-type MHC class I antigens after liver transplantation in the rat. Transplant Proc. 1993 Oct;25(5):2858–2858. [PubMed] [Google Scholar]
  13. Kobayashi E., Kamada N., Enosawa S., Toyama N., Delriviere L., Goto S., Lord R., Stamatiou S., Miyata M. A technique for complete thymectomy in adult rats. J Immunol Methods. 1994 May 2;171(1):33–36. doi: 10.1016/0022-1759(94)90225-9. [DOI] [PubMed] [Google Scholar]
  14. Kyewski B. A., Fathman C. G., Kaplan H. S. Intrathymic presentation of circulating non-major histocompatibility complex antigens. Nature. 1984 Mar 8;308(5955):196–199. doi: 10.1038/308196a0. [DOI] [PubMed] [Google Scholar]
  15. Larsen C. P., Steinman R. M., Witmer-Pack M., Hankins D. F., Morris P. J., Austyn J. M. Migration and maturation of Langerhans cells in skin transplants and explants. J Exp Med. 1990 Nov 1;172(5):1483–1493. doi: 10.1084/jem.172.5.1483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lo D., Burkly L. C., Widera G., Cowing C., Flavell R. A., Palmiter R. D., Brinster R. L. Diabetes and tolerance in transgenic mice expressing class II MHC molecules in pancreatic beta cells. Cell. 1988 Apr 8;53(1):159–168. doi: 10.1016/0092-8674(88)90497-7. [DOI] [PubMed] [Google Scholar]
  17. Lord R., Goto S., Kobayashi E., Kamada N., Sunagawa M. Detection of membrane-bound and soluble MHC class I antigen from donor migrating cells following rat liver transplantation. Transpl Immunol. 1994 Jun;2(2):94–98. doi: 10.1016/0966-3274(94)90034-5. [DOI] [PubMed] [Google Scholar]
  18. Morahan G., Allison J., Miller J. F. Tolerance of class I histocompatibility antigens expressed extrathymically. Nature. 1989 Jun 22;339(6226):622–624. doi: 10.1038/339622a0. [DOI] [PubMed] [Google Scholar]
  19. Park S. K., Brody J. I., Wallace H. A., Blakemore W. S. Immunosuppressive effect of surgery. Lancet. 1971 Jan 9;1(7689):53–55. doi: 10.1016/s0140-6736(71)90777-x. [DOI] [PubMed] [Google Scholar]
  20. Perico N., Rossini M., Imberti O., Remuzzi G. Evidence of the central role of the thymus in the induction of donor-specific unresponsiveness to a renal allograft. Transplantation. 1992 Nov;54(5):943–945. doi: 10.1097/00007890-199211000-00038. [DOI] [PubMed] [Google Scholar]
  21. Remuzzi G., Rossini M., Imberti O., Perico N. Kidney graft survival in rats without immunosuppressants after intrathymic glomerular transplantation. Lancet. 1991 Mar 30;337(8744):750–752. doi: 10.1016/0140-6736(91)91368-5. [DOI] [PubMed] [Google Scholar]
  22. Starzl T. E., Demetris A. J., Murase N., Ildstad S., Ricordi C., Trucco M. Cell migration, chimerism, and graft acceptance. Lancet. 1992 Jun 27;339(8809):1579–1582. doi: 10.1016/0140-6736(92)91840-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Starzl T. E., Demetris A. J., Murase N., Thomson A. W., Trucco M., Ricordi C. Donor cell chimerism permitted by immunosuppressive drugs: a new view of organ transplantation. Immunol Today. 1993 Jun;14(6):326–332. doi: 10.1016/0167-5699(93)90054-o. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Starzl T. E., Demetris A. J., Trucco M., Murase N., Ricordi C., Ildstad S., Ramos H., Todo S., Tzakis A., Fung J. J. Cell migration and chimerism after whole-organ transplantation: the basis of graft acceptance. Hepatology. 1993 Jun;17(6):1127–1152. [PMC free article] [PubMed] [Google Scholar]
  25. Starzl T. E., Demetris A. J., Trucco M., Ramos H., Zeevi A., Rudert W. A., Kocova M., Ricordi C., Ildstad S., Murase N. Systemic chimerism in human female recipients of male livers. Lancet. 1992 Oct 10;340(8824):876–877. doi: 10.1016/0140-6736(92)93286-v. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES