Summary
Parabiosed inbred LEW/MAI- and CDF-rats were subjected to immunosuppressive therapy for 7–11 days: They were given intraperitoneally a total amount of 68–85 mg/kg (Vg I) or 40–51 mg/kg cyclophosphamide (Vg II). All animals of the untreated group Kg 0 died with typical symptoms of parabiotic disease, 10 out of 13 within 14 days. Most CDF-partners in Vg I died during the 2nd week due to overdosage. In Vg II 12 out of 16 pairs survived more than 4 weeks in parabiosis, 9 of them were separated in good general condition after 31–54 days. The vascular anastomoses were open, the tissue bridges delicate. There was a highly significant decrease in lymphocytes in Kg 0 (3100±800 on the 10th day). In Vg II subnormal values were recorded for weeks after discontinuance of the CY-treatment (6400±770 on the 30th day); normal values were found after separation. 10–18 days after separation skin-transplantations were performed: sensitization was found in only 2 out of 9 CDE-rats, as expressed by accelerated rejection; 3 out of 9 showed delayed rejection. There was normal rejection of transplants of a different strain. Partner-transplants were rejected as “white grafts≓ by 2 Lewis-rats which were living in parabiosis for 36 days in good general condition and with open vascular anastomoses. The results are discussed as expression of relative inefficiency of parabiosis for induction of immunological transplant-tolerance, because long-lasting tolerance could be achieved in the same strain combination using the same immunosuppressive drug by short term cross-transfusion via cannulation of large vessels.
Zusammenfassung
Parabiosierte LEW/MAI- und CDP-Inzuchtratten wurden 7–11 Tage i.p. mit gesamt 68–85 mg/kg Cyclophosphamid (Vg I) bzw. 40 bis 51 mg/kg Cyclophosphamid (Vg II) immunosuppressiv behandelt. In der unbehandelten Kontrollgruppe (Kg 0) starben alle Paare mit typischen Symptomen der Parabiosekrankheit, 10 von 13 binnen 14 Tagen. In Vg I starben die meisten CDF-Partner infolge überdosierung in der 2. Woche. In Vg II lebten 12 von 16 Paaren länger als 4 Wochen in Parabiose: 9 wurden nach 31–54 Tagen in gutem Allgemeinzustand separiert, die Gefä\anastomosen waren offen, die Gefä\brücken zart. Die Lymphocytenwerte waren in Kg 0 hochsignifikant erniedrigt (3100±800 am 10. Tag), in Vg II waren sie nach Restitution von der CY-Behandlung wochenlang subnormal (6400±770 am 30. Tag) und normalisierten sich nach Separation. Hauttransplantate wurden 10–18 Tage nach Separation durchgeführt: 2 von 9 CDF-Ratten erwiesen sich als sensibilisiert, d. h. stie\en Lewis-Transplantate beschleunigt ab, 3 von 9 zeigten Absto\ungshemmung; Kontrolltransplantate von einem Fremdstamm wurden normal abgesto\en. 2 seit 36 Tagen in Parabiose stehende und bei gutem Allgemeinzustand und offenen Gefä\brücken weitere 3 Wochen (bis zur Separation) gebliebene Lewis-Ratten stie\en Partnertransplantate als „white grafts“ ab. Die Ergebnisse werden als Ausdruck relativer Inefflzienz der Parabiose zur Induktion immunologischer Transplantattoleranz diskutiert, da in derselben Stammkombination mit demselben Immunosuppressivum lang anhaltende Toleranz durch kurzfristige Kreuztransfusion über Gefä\katheter erzielt werden konnte.
Similar content being viewed by others
Literatur
Anderson, D., Billingham, R. E., Lampkin, G. H., Medawar, P. B.: The use of skin grafting to distinguish between monozygotic and dizygotic twins in cattle. Heredity5, 379 (1951).
Cornelius, E. A., Yunis, E. J., Martinez, C.: Parabiosis intoxication: Clinical, haematologic, and serologic features. Transplantation5, 112 (1967).
Elkins, W. L., Palm, J.: Identification of a single strong histocompatibility locus in the rat by normal spleen-cell transfer. Ann. N.Y. Acad. Sci.129, 573 (1966).
Gowland, G.: Induction of transplantation tolerance in adult animals. Brit. med. Bull.21, 123 (1965).
Hašek, M.: Parabiosis in birds during embryonic development. Czech. Biol.2, 25 (1953).
Letterer, E.: über Amyloid bei Parabiose. Dtsch. med. Wschr.88, 2527 (1963).
Mariani, T., Martinez, C., Smith, M., Good, R. A.: Induction of immunologic tolerance to male skin isografts in female mice subsequent to the neonatal period. Proc. Soc. exp. Biol. Med.101, 596 (1959).
McBride, R. A., Simonsen, M.: Cellular and humoral phenomenas during the inductive phase of parabiosis tolerance. Transplantation3, 140 (1965).
—, Nisbet, N. W., Skowron-Cendrzak, A.: Rate of cross-circulation in parabiosis: Its significance, relationship to genetic disparity, and experimental modification. Transplantation5, 569 (1967).
Müller-Ruchholtz, W.: Immunologische Folgen fortgesetzter Kreuztransfusionen. Habilitationsschrift, Universität Kiel 1966.
-: Short-term immunosuppression and cross-transfusion for induction of immunological tolerance of skin grafts. II. Internat. Congr. Transpl. Soc. New York 1968.
- Borchers, V.: in Vorbereitung (1969).
—, Gundermann, K. O.: Einfacher Farbtest zur Erkennung der Durchblutung von Hauttransplantaten in vivo. Z. Immun.-Forsch.127, 450 (1964).
Myburgh, J. A.: Repeated parabiosis in mice: Immunological and haematological sequelae, and demonstration of hybrid-anti-parent reaction. Transplantation6, 400 (1968).
Nakić, B., Kastelan, A., Mikuska, J., Bunarevik, A.: Quantitative analysis of chimaeric state in mice. II. Immunology12, 615 (1967).
Owen, R. D.: Immunogenetic consequences of vascular anastomosis between bovine twins. Science102, 400 (1945).
Shapiro, F., Martinez, C., Smith, J. M., Good, R. A.: Tolerance of skin homografts induced in adult mice by multiple injections of homologous spleen cells. Proc. Soc. exp. Biol. Med.106, 472 (1961).
Simonsen, M.: In: Mechanisms of Immunological Tolerance. London: Academic Press 1962a.
—: Graft-versus-host reactions. Their natural history and applicability as tools of research. Progr. Allergy6, 349 (1962b).
Skowron-Cendrzak, A.: Facilitation of homograft tolerance in parabiotic mice by treatment with amethopterin. Transplantation2, 478 (1964).
Stark, O., Zeiss, I.: Immunologisch definierte Ratteninzuchtstämme in transplantationsbiologischen Versuchen. 1. Tagg. Ges. Immunol. Freiburg, Okt. 1969.
Thiede, A.: über den Einflu\ kurzfristiger Cyclophosphamidbehandlung auf Histoincompatibilitätsreaktionen bei allogenetischen Ratten-Parabiosen. Inaugural-Dissertation, Universität Kiel 1968.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Thiede, A., Müller-Ruchholtz, W. Wirkung temporärer Cyclophosphamidbehandlung auf allogene Rattenparabiosen. Z. Gesamte Exp. Med. 151, 321–330 (1969). https://doi.org/10.1007/BF02052921
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02052921