QUANTITATIVE-ANALYSIS OF PROINFLAMMATORY AND ANTIINFLAMMATORY CYTOKINE MESSENGER-RNA IN NEURAL GRAFT-REJECTION

The central nervous system (CNS) has been considered an immunologicall y privileged site. However, this concept is now changing because rejec tion of histoincompatible neural grafts is commonly observed in the CN S. To be able to use neural transplantation as therapy for human disea ses, it is important to determine factors that are related to brain-gr aft rejection. In the present study, we examined the phenotype of infi ltrating T cells around grafts in the cerebra that had received xenoge neic (mouse to rat) neural transplants. Furthermore, the amount of pro - and anti-inflammatory cytokine mRNA was determined by competitive PC R at various time points after the neural transplantation. Immunohisto chemical examination revealed that both CD4-positive and CD8-positive T cells infiltrated the CNS parenchyma. In competitive PCR analysis, l evels of IFN-gamma and perforin in xenografts on days 10 and 13 post-t ransplantation (PT) were higher than those in isografts (rat to rat) a t the same stage, whereas the levels of TNF-alpha, which was detected only on day 7 PT, were not significantly different between the two gro ups. With regard to anti-inflammatory cytokines, TGF-beta 1 mRNA was r ecognized throughout the examination period, but there was no signific ant difference between xeno- and iso-grafts at most time points. These findings suggest that IFN-gamma and perforin secreted by infiltrating CD4-positive and CD8-positive T cells, respectively, play an importan t role in neural graft rejection. The responses of anti-inflammatory c ytokines seem to be nonspecific reactions to grafts or surgical proced ures. (C) 1998 Elsevier Science B.V. All rights reserved.