Cellular immune reactions in brain transplantation: effects of graft pooling and immunosuppression in the 6-hydroxydopamine rat model of Parkinson's disease.
We used high immunogenic mouse and low immunogenic rat brain transplants to investigate the effect of pooling of tissue with immunogenetic disparity on cellular immune reactions. Foetal xenogenic mouse striatum and allogenic rat substantia nigra were implanted into i) the 6-hydroxydopamine lesioned striatum of outbred female Sprague-Dawley rats as a pooled cell suspension, or into ii) the unlesioned and lesioned striata as non-pooled separate deposits, with or without immunosuppressive treatment with cyclosporin A (Cy A). In control animals, iii) mouse striatum was replaced by rat striatum, and iv) sham grafts with and without immunosuppression. Six weeks post grafting, brains were semiquantitatively processed using immunocytochemical markers for microglia, astrocytes, T-helper cells, and macrophages, major histocompatibility class (MHC) I and II expression. The total amount of immunoreactivity (PA) for microglial cells and astrocytes was pronounced and the PA for T-helper cells and macrophages was doubled in recipients of pooled rat and mouse cografts compared to non-pooled deposits, indicating ongoing immune reactions with participation of glial cells. MHC I expression was significantly increased in pooled xeno- and allogenic cografts with and without immunosuppression compared to allogenic controls. Expression of MHC II was significantly increased in pooled cografts without immunosuppression. In recipients of separate, non-pooled heteroimmunogenic cotransplants, MHC I and II expression was significantly increased in xenogenic deposits with and without immunosuppression. MHC II was as well significantly increased in allogenic deposits without immunosuppression. Immunosuppressed animals with non-pooled allogenic mouse cografts showed low levels of cellular immune parameters. In conclusion non-pooled heteroimmunogenic grafts lead to less pronounced immune reactions compared to pooled grafts and immunosuppressive treatment with Cy A has a beneficial effect on acute transplant-associated immune parameters.
Schwarz
S C
SC
Department of Neurology, Klinikum Grosshadern, Munich, Germany.
Kupsch
A R
AR
Banati
R
R
Oertel
W H
WH
D000818:Animals; D016380:Brain Tissue Transplantation / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007165:Immunosuppression Therapy; D051379:Mice; D017628:Microglia / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology*; D010300:Parkinson Disease / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016627:Oxidopamine