Immunological reaction and blood-brain barrier in mouse-to-rat cross-species neural graft.

Pieces of brainstem tissue from mouse embryos were transplanted into the cerebellar vermis of 49 adult rats, which had or which had not been treated with Cyclosporin A (10 mg/kg/day). With no treatment of immunosuppressants survival rates of xenografts were low. However, when Cyclosporin A was administered, the rates increased from 40% (4/10) to 67% (8/12) 2 weeks after grafting and from 25% (3/12) to 60% (9/15) 4 weeks after grafting, although immunological reactions of varying severities were noted in all of the surviving grafts. The present immunocytochemical study elucidated the composition of cell infiltrations frequently seen in the grafts. The results showed that a large number of cytotoxic/suppressor T lymphocytes appeared, while the numbers of helper/inducer T lymphocytes were relatively small. In addition, increased staining of astrocytes and microglia was observed in areas of cell infiltration. These activated cells might play a certain role in the process of graft rejection in the brain. Formation of the blood-brain barrier in the xenografts was examined by means of peroxidase cytochemistry and immunohistochemistry. In brains containing surviving grafts limited leakage of peroxidase, following its injection into the host systemic circulation 30-75 min prior to sacrifice, was detectable at the graft-host interface and at the operation scar near the pial surface. In brains containing rejected grafts extensive extravasation of peroxidase was detected. The severity of the immunological reaction was correlated with the intensity of the rupture in the blood-brain barrier. The findings suggested that the immunological reaction contributed to the transendothelial permeability changes in the vessels of brains containing rejected grafts.