ULTRASTRUCTURAL STUDIES OF AN IMMUNE-MEDIATED INFLAMMATORY RESPONSE IN THE CNS PARENCHYMA DIRECTED AGAINST A NON-CNS ANTIGEN

We have shown previously that heat-killed bacillus Calmette-Guerin inj ected into the brain parenchyma becomes sequestered behind the blood-b rain barrier for months undetected by the immune system. However, inde pendent peripheral sensitization of the immune system to bacillus Calm ette-Guerin results in recognition of bacillus Calmette-Guerin in the brain and the induction of focal chronic lesions [Matyszak M. K. and F erry V. H. (1995) Neuroscience 64, 967-977]. We carried out ultrastruc tural studies of these lesions. Prior to subcutaneous challenge we use d immunohistochemistry to detect bacillus Calmette-Guerin which was fo und in cells with the morphology of macrophages/microglia and in periv ascular macrophages. Eight to 14 days after subcutaneous challenge the re was a conspicuous leucocyte infiltration at the site of bacillus Ca lmette-Guerin deposits within the brain parenchyma. The majority of th ese cells were macrophages and lymphocytes, with some lymphocytes show ing characteristic blast morphology. Dendritic cells in close contact with lymphocytes were prominent. Inflammatory cells were found in peri vascular cuffs and within the brain parenchyma. The tissue was oedemat ous and some axons were undergoing Wallerian degeneration with associa ted myelin degeneration. Throughout the lesions, but more commonly at the edges, we detected macrophages containing myelin in their cytoplas m close to intact axons and axons with evidence of remyelinating sheat hs, suggestive of primary demyelination. In older lesions, two to thre e months after the peripheral challenge, the oedema was less pronounce d and there was little evidence of Wallerian degeneration. There were still many macrophages, lymphocytes and dendritic cells, although the number of these cells was lower than in earlier lesions. Late lesions also contained many plasma cells which were not present in early lesio ns. In these late lesions there were bundles of axons with no myelin o r a few axons with thin myelin sheaths, suggestive of persistent or on going demyelination or remyelination. These observations show that, du ring a delayed-type hypersensitivity lesion in the CNS, the leucocyte populations change with time, and suggest that the mechanisms and type of tissue damage are different in the early and late stages of the le sion. (C) 1997 IBRO. Published by Elsevier Science Ltd.