Log in

Intrathymic inoculation of donor liver specific antigen alleviates rejection of liver allotransplantation

  • Biomedicine
  • Published:
Journal of Zhejiang University-SCIENCE A Aims and scope Submit manuscript

Abstract

Use and effects of liver specific antigen in orthotopic liver transplantations were researched in this study. Group I: syngeneic control (Wistar-to-Wistar); Group II: acute rejection (SD-to-Wistar); Group III: Thymic inoculation of SD rat LSA day 7 before transplantation. The observation of common situation and survival time, rejection grades, NF-κB activity of splenocytes and IL-2mRNA expression of grafted liver were used to analyze acute rejection severity and immune state of animals in different groups. The common situation of group I was very well after transplantation and no signs of rejection were found. Recipients of group II lost body weight progressively All dead within day 9 to day 13 posttransplantation; median survival time was 10.7 ±0.51 days. It was an optimal acute rejection control. As for group III, 5 out of 6 recipients survived for a long time and common situation was remarkably better than that of group II. Its rejection grades were significantly lower than that of group II(P<0.05). NF-κB activity was only detected in group I at day 5 and day 7 after transplantation, whereas high activity of NF-κB was detected at all time points in groupII and the low NF-κB activity detected in group III was significantly lower than that of group II (P<0.05). No IL-2mRNA expression was detected at any time point in group I, whereas high level expression was detected at all time points in group II and the low level expression only detected at day 3 in group III was significantly lower than that of group II (P<0.05). Conclusion: LSA is an important transplantation antigen which is involved directly in the immunorejection of liver transplantation. We report here for the first time that intrathymic inoculation of LSA can alleviate the rejection of liver allotransplantation; and that grafts can survive for a long time thereby, thus leading to a novel way to achieve liver transplantation immunotolerance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bishop, G. A., Sun, J., Sheil, A. G. and McCaughan, G. W., 1997. High-dose/activation-associated tolerance: a mechanism for allograft tolerance.Transplantation,64: 1377–1382.

    Article  Google Scholar 

  • Donaldson, P., Underhill, J., Doherty, D., Hayllar, K., Calne, R., Tan, K. C., O'Grady, J., Wight, D., Portmann, B. and Williams, R., 1993. Influence of human leukocyte antigen matching on liver allograft survival and rejection: “the dualistic effect”.Hepatology,17: 1008–1015.

    Article  Google Scholar 

  • Doran, T. J., Derley, L., Chapman, J., McCaughan, G., Painter, D., Dorney, S. and Sheil, A. G., 1992. Severity of liver transplantation rejection is associated with recipient HLA type.Transplant Proc,24: 192–193.

    Google Scholar 

  • Kalli, K., Huntoon, C., Bell, M. and McKean, D. J., 1998. Mechanism responsible for T cell antigen receptor and CD28-or interleukin 1 (IL-1) receptor-initiated regulation of IL-2 gene expression by NF-κB.Mol cell boil,18 (6): 3140–3148.

    Article  Google Scholar 

  • Kamada, N. and Calne, R. Y., 1983. A surgical experience with five hundred thirty liver transplants in the rat.Surgery,93: 64–69.

    Google Scholar 

  • Kemnitz, J., Ringe, B., Cohnert, T. R., Gubernatis, G., Choritz, H. and Georgii, A., 1989. Bile duct injury as a part of diagnostic criteria for liver allograft rejection.Hum Pathol,20(2): 132–143.

    Article  Google Scholar 

  • Kravchenko, V. V., Pan, Z., Han, J., Herbert, J. M., Ulevitch, R. J. and Ye, R. D., 1995. Platelet-activating factor induces NF-kappa B activation through a G protein-coupled pathway.J Biol Chem,270(25): 14928–14934.

    Article  Google Scholar 

  • Lau, H., Reemtsma, K. and Hardy, M. A. 1983. Pancreatic islet allograft prolongation by donor-specific blood transfusions treated with ultraviolet irradiation.Science,221(4612): 754–756.

    Article  Google Scholar 

  • Liblau, R. S., Tisch, R., Shokat, K., Yang, X., Dumont, N., Goodnow, C. C. and McDevitt, H. O., 1996. Intravenous injection of soluble antigen induces thymic and peripheral T-cells apoptosis.Proc Natl Acad Sci USA,93: 3031–3036.

    Article  Google Scholar 

  • Lohse, A. W., Meyer, Z., Buschenfelde, K. H., 1994. Experimental Hepatitis.In: Cohen IR, Miller A, eds. Autoimmune Disease Models: A Guidebook. Academic Press, San Diego, p. 191–199.

    Chapter  Google Scholar 

  • Markus, B. H., Duquesnoy, R. J., Gordon, R. D., Fung, JJ., Vanek, M., Klintmalm, G., Bryan, C., Van Thiel, D. and Starzl, T. E., 1988. Histocompatibility and liver transplant outcome. Does HLA exert a dualistic effect?Transplantation,46(3): 372–377.

    Google Scholar 

  • Oluwole, S. F., Chowdhury, N. C. and **, M. X., 1994. The relative contribution of intrathymic inoculation of donor leukocyte subpopulations in the induction of specific tolerance.Cell Immunol,153: 163–170.

    Article  Google Scholar 

  • Oluwole, S. F., **, M. X., Chowdhury, N. C. and Ohajekwe, O. A., 1994. Effectiveness of intrathymic inoculation of soluble antigens in the induction of specific unresponsiveness to rat islet allografts without transient recipient immunosuppression.Transplantation,58 (10): 1077–1081.

    Article  Google Scholar 

  • Patric, A. B. and Devid, B., 1996. NF-κB: ten years after.Cell,87(1): 13–20.

    Article  Google Scholar 

  • Sharland, A., Shastry, S., Wang, C., Rokahr, K., Sun J., Sheil, A. G., McCaughan, G. W. and Bishop, G. A., 1998. Kinetics of intragraft cytokine expression, cellular infiltration, and cell death in rejection of renal allografts compared with acceptance of liver allografts in a rat model: early activation and apoptosis is associated with liver graft acceptance.Transplantation,65(10): 1370–1377.

    Article  Google Scholar 

  • Stadlbauer, T. H., Schaub, M., Magee, C. C., Kupiec Weglinski, J. W. and Sayegh, M. H., 2000. Intrathymic immunomodulation in sensitized rat recipients of cardiac allografts: requirements for allorecognition pathways.J Heart Lung Transplant,19(6): 566–575.

    Article  Google Scholar 

  • Van Antwerp, D. J., Martin, S. J., Kafri, T., Green, D. R. and Verma, I. M., 1996. Suppression of TNF-alpha-induced apoptosis by NF-kappaB.Science,274(5288): 787–789.

    Article  Google Scholar 

  • Yan, Y. H. and Liu, G. Z., 1998. Transplantation antigens.In: Chenshi, Transplantation Immunology. Hubei Science and Technology Press, Wuhan, p. 45–47 (in Chinese).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jia Chang-ku.

Additional information

Project (NO. 011106206) supported by the Science and Technology Bureau of Zhejiang Province Foundation

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jia, Ck., Zheng, Ss. & Zhang, Ab. Intrathymic inoculation of donor liver specific antigen alleviates rejection of liver allotransplantation. J. Zhejiang Univ. Sci. A 4, 485–490 (2003). https://doi.org/10.1631/jzus.2003.0485

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1631/jzus.2003.0485

Key words

Document code

CLC number

Navigation