Immunosuppression for neural xenografts: a comparison of cyclosporin and anti-CD25 monoclonal antibody.
OBJECTIVE
The goal of this study was to compare the effects of short- and long-term immunosuppression induced by cyclosporin with those of immunosuppression induced by a monoclonal antibody against the rat interleukin-2 receptor (anti-CD25 mAb) in rats with xenografts.


METHODS
The authors compared the in vivo function and final histological characteristics of fetal mouse mesencephalon xenografts in hemiparkinsonian rats in which immunosuppression was induced by: 1) a short course (2 weeks) of cyclosporin; 2) a long course (8 weeks) of cyclosporin; or 3) a short course of treatment with anti-CD25 mAb. Adult Wistar rats were unilaterally lesioned with 6-hydroxydopamine in their medial forebrain bundle, after which their rotational behavior in response to methamphetamine was quantified. Four groups of 20 rats with rotations numbering greater than six turns per minute received fetal mouse mesencephalon transplants to their dopamine-denervated striatum. Group 1 received no immunosuppression therapy; Group 2 received daily intraperitoneal injections of 10 mg/kg cyclosporin for 2 weeks; Group 3 received daily intraperitoneal injections of 10 mg/kg cyclosporin for 8 weeks; and Group 4 received daily intraperitoneal injections of 1 mg/kg anti-CD25 mAb for 2 weeks. The rats were tested for rotational behavior every 4 weeks and killed after 16 weeks. Surviving xenografts were assessed using immunohistochemical staining for a mouse neuronal marker (Thy-1.2). Sixteen weeks after transplant, there were significantly more surviving xenografts in Groups 3 (p < 0.001) and 4 (p < 0.001) compared with control Group 1 (Fisher's exact test) and significantly better functioning xenografts in Groups 3 (p < 0.01) and 4 (p < 0.05) compared with control Group 1 (contrasts of groups following analysis of variance with Bonferroni correction).


CONCLUSIONS
A short course of anti-CD25 mAb-induced immunosuppression was as effective as a long course of cyclosporin-induced immunosuppression in this model.
Honey
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CR
Division of Neurosurgery, University of British Columbia, Vancouver, Canada.
Shen
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016332:Fetal Tissue Transplantation; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008636:Mesencephalon / Q000637:transplantation*; D051379:Mice; D010302:Parkinson Disease, Secondary / Q000601:surgery; D051381:Rats; D017208:Rats, Wistar; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D016572:Cyclosporine