Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Experimental immuno-alteration

  • 11 Accesses

  • 40 Citations

Abstract

In the past few years, remarkable advances have been made in preventing rejection of islet allografts and xenografts (rat to mouse) by 6 procedures which do not involve continuous immunosuppressive therapy of recipient rodents. Four methods alter or destroy passenger lymphoid cells in the islets prior to transplantation. These include in vitro culture of donor rat islets at low temperature and a single injection of anti-lymphocyte serum in the recipients, culture of rat or mouse islet aggregates in 95% O2, and pretreatment of mouse islets with Ia antibody and complement or with a monoclonal antidendritic cell antibody and complement. Two methods induce partial tolerance in recipients by preimmunization with donor blood treated either with Ia antibody and complement or ultraviolet irradiation. These preimmunization procedures permit the use of untreated donor islets.

Two methods have been developed for the mass isolation of canine islets. Initial studies indicate that low-temperature culture of donor canine islets and a single injection of anti-lymphocyte serum will prevent rejection of canine islet allografts. The technical problems remaining for human islet allografts are selection of the optimum method of preventing islet allograft rejection based on studies in the dog, adaptation of the mass islet isolation techniques to the human pancreas, and selection of a safe and optimum site for transplantation.

Résumé

En quelques années, la prévention du rejet des hétéro et xénogreffes d'îlots (greffons de rats sur des souris) vient de réaliser des progrès considérables grâce à six procédés différents qui n'impliquent pas de traitement immunosuppresseur chez les rongeurs receveurs. Quatre de ces méthodes modifient ou détruisent les lymphocytes passagers dans les îlots avant la transplantation. Elles comprennent la culture in vitro à basse température des îlots du rat donneur associée à une injection unique de sérum anti-lymphocytaire chez les receveurs; la culture d'îlots de rat ou de souris sous 95% d'oxygène; le pré-traitment des îlots de souris par un anticorps anti-Ia et le complément ou par un anticorps monoclonal anti-cellule dendritique, et le complément.

Deux procédés ont été mis au point pour isoler en grande quantité les îlots de chien. Des études préliminaires chez le chien montrent que la culture des îlots à basse température, associée à une injection unique de sérum anti-lymphocytaire, suffit à prévenir le rejet d'une hétérogreffe d'îlots. Les problèmes techniques restant à résoudre pour la greffe d'îlots chez l'homme sont de trois ordres: le choix de la méthode de prévention du rejet, en se fondant sur les résultats obtenus chez le chien; l'adaptation au pancréas humain des procédés d'extraction d'îlots en grande quantité; et la sélection d'un site de transplantation qui soit à la fois sûr et optimal quant à son efficacité.

Resumen

En los Ultimos años se han logrado adelantos importantes en la prevención del rechazo de aloinjertos y xenoinjertos (ratón a rata) de islotes de Langerhans por seis métodos que excluyen terapia inmunosu-presora continua en recipientes roedores. Cuatro métodos alteran o destruyen en los islotes las “celulas linfoides pasajeras” (células dendríticas) previo al transplante. Estos cuatro métodos incluyen el cultivo en vitro a baja temperatura de islotes de ratas donantes y una inyección de suero antilinfocítico al recipiente; el cultivo mixto de islotes de rata y raton en 95% O2; el tratamiento previo con anticuerpo Ia y complemento de islotes de ratón; o tratamiento previo con anticuerpo monoclonal contra células dendríticas y complemento. Los otros dos métodos incluyen la inducción en el recipiente de la tolerancia parcial por la preinmunización con sangre del donante tratada con anticuerpo Ia y complemento, o por la irradiación ultravioleta. Estos métodos de preinmunización permite el uso de islotes previamente no tratados.

Se han desarrollado dos métodos para el aislamiento en grandes cantidades de islotes caninos. Investigaciones preliminares demuestran que el cultivo de islotes del donante a baja temperatura, acompañado con una sola inyección de suero antilinfocitico al recipiente, evita el rechazo de aloinjertos en perros. Basado en estos estudios en perros, los problemas técnicos restantes para los aloinjertos de islotes en humanos son: la selección del método óptimo para la prevención del rechazo, la adaptación de tećnicas de aislamiento de islotes en masa al pancreas humano y la selección del sitio óptimo y mas seguro para la implantación del aloinjerto.

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

References

  1. 1.

    Snell, G.D.: The homograft reaction. Ann. Rev. Microbiol.2:439, 1957

  2. 2.

    Lafferty, K.J., Cooley, M.A., Woolnough, J., Walker, K.Z.: Thyroid allograft immunogenicity is reduced after a period in organ culture. Science188:259, 1975

  3. 3.

    Lacy, P.E., Davie, J.M., Finke, E.H., Scharp, D.W.: Prolongation of islet allograft survival. Transplantation27:171, 1979

  4. 4.

    Lacy, P.E., Davie, J.M., Finke, E.H.: Prolongation of islet allograft survival following in vitro culture (24°C) and a single injection of ALS. Science204:312, 1979

  5. 5.

    Opelz, G., Terasaki, P.I.: Lymphocyte antigenicity loss with retention of responsiveness. Science184:464, 1974

  6. 6.

    Lacy, P.E., Davie, J.M., Finke, E.H.: Induction of rejection of successful allografts of rat islets by donor peritoneal exudate cells. Transplantation28:415, 1979

  7. 7.

    Lacy, P.E., Davie, J.M., Finke, E.H.: Prolongation of islet xenograft survival without continuous immu-nosuppression. Science209:283, 1980

  8. 8.

    Lacy, P.E., Davie, J.M., Finke, E.H.: Prolongation of islet xenograft survival (rat to mouse). Diabetes30:285, 1981

  9. 9.

    Faustman, D., Hauptfeld, V., Davie, J.M., Lacy, P.E., Shreffler, D.C.: Murine pancreatic β-cells express H-2K and H-2D but not Ia antigens. Proc. Natl. Acad. Sci. USA78:1563, 1981

  10. 10.

    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. USA78:5156, 1981

  11. 11.

    Zitron, I.M., Ono, J., Lacy, P.E., Davie, J.M.: Active suppression in the maintenance of pancreatic islet allografts. Transplantation32:156, 1981

  12. 12.

    Faustman, D., Hauptfeld, V., Lacy, P., Davie, J.: Demonstration of active tolerance in maintenance of established islet of Langerhans allografts. Proc. Natl. Acad. Sci. USA79:4153, 1982

  13. 13.

    Faustman, D., Lacy, P., Davie, J., Hauptfeld, V.: Prevention of allograft rejection by immunization with donor blood depleted of la-bearing cells. Science217:157, 1982

  14. 14.

    Lau, H., Reemtsma, K., Hardy, M.A.: Pancreatic islet allograft prolongation by donor-specific blood transfusions treated with ultraviolet irradiation. Science221:754, 1983

  15. 15.

    Bowen, K.M., Lafferty, K.J.: Reversal of diabetes by allogeneic islet transplantation without immuno-suppression. Aust. J. Exp. Biol. Med. Sci.58:441, 1980

  16. 16.

    Janney, C.G., Davie, J.M., Lacy, P.E., Finke, E.H.: Characterization of lymphocytes from rejected and nonrejected islet xenografts. Transplantation33:585, 1982

  17. 17.

    Steinman, R.M., Nussenzweig, M.C.: Dendritic cells: Features and functions. Immunol. Rev.53:127, 1980

  18. 18.

    Steinman, R.M., Witmer, M.D.: Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. Proc. Natl. Acad. Sci. USA75:5132, 1978

  19. 19.

    Nussenzweig, M.C., Steinman, R.M., Witmer, M.D., Gutchinov, B.: A monoclonal antibody specific for mouse dendritic cells. Proc. Natl. Acad. Sci. USA79:161, 1982

  20. 20.

    Steinman, R.M., Gutchinov, B., Witmer, M.D., Nussenzweig, M.C.: Dendritic cells are the principal stimulators of the primary mixed leukocyte reaction in mice. J. Exp. Med.157:613, 1983

  21. 21.

    Bobzien, B., Yasunami, Y., Majercik, M., Lacy, P.E., Davie, J.M.: Intratesticular transplants of islet xenografts (rat to mouse). Diabetes32:213, 1983

  22. 22.

    Yasunami, Y., Lacy, P.E., Finke, E.H.: A new site for islet transplantation—a peritoneal-omental pouch. Transplantation36:181, 1983

  23. 23.

    Lacy, P.E., Kostianovsky, M.: A method for isolation of intact islets of Langerhans from the rat pancreas. Diabetes16:35, 1967

  24. 24.

    Lacy, P.E., Lacy, E.T., Finke, E.H., Yasunami, Y.: An improved method for the isolation of islets from the beef pancreas. Diabetes31:109, 1982

  25. 25.

    Lacy, P., Finke, E.H., Gebel, H., Scharp, D.: A method for the mass isolation of islets from the canine pancreas. Presented at the 19th Annual Meeting of the European Association for the Study of Diabetes, September 14–17, 1983, Oslo, Norway

  26. 26.

    Long, J.A., Britt, L.D., Olack, B.J., Scharp, D.W.: Autotransplantation of isolated canine pancreatic islet cells. Transplant. Proc.15:1332, 1983

Download references

Author information

Correspondence to Paul E. Lacy M.D., Ph.D..

Additional information

Supported in part by NIH PHS grant number AM01226; the Kroc Foundation; Brown and Williamson Tobacco Corporation, Phillip Morris Incorporated, R.J. Reynolds Tobacco Company, United States Tobacco Company; and the United Parcel Service Foundation.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lacy, P.E. Experimental immuno-alteration. World J. Surg. 8, 198–203 (1984). https://doi.org/10.1007/BF01655135

Download citation

Keywords

  • Mouse Islet
  • Islet Isolation
  • Islet Allograft
  • Mass Islet
  • Permite