The immunopathology of adoptively transferred experimental allergic encephalomyelitis (EAE) in Lewis rats. Part 1. Immunohistochemical examination of developing lesions of EAE

Abstract

In order to examine developing lesions of experimental allergic encephalomyelitis (EAE) at the preclinical stage, adoptive transfer of EAE was achieved in Lewis rats using spleen cells obtained from rats previously immunized with 50 micrograms of guinea pig myelin basic protein (MBP) in complete Freund's adjuvant. After cell transfer, all the recipient rats developed severe paraparesis with minimal variation in the onset of clinical signs, which facilitated immunohistochemical examination of developing lesions of EAE in asymptomatic animals. The initial pathological finding detected in this system was an increased number of inflammatory cells (both OX19+ and OX8+ T cells and macrophages) in the subarachnoid space (SAS) which was observed on day 3 post-transfer (PT) when the recipient animals showed no neurological abnormalities. By day 4 PT, inflammatory cells were detected in the Virchow-Robin space of vessels which were continuous to the SAS. Perivascular lymphocytic infiltration was scarcely detected in the gray matter. On day 5 PT, the rats showed severe paraparesis. Inflammatory foci increased in number and were detected in both the white and gray matter. Diffuse parenchymal T-lymphocyte infiltration was also recognized at this stage. From day 6 PT onwards, inflammatory cells decreased gradually. On day 8 PT, all the rats recovered from EAE and few inflammatory cells were detected in the parenchyma and SAS. Immunohistochemical examination of T-cell subsets and Ia antigens revealed that the number of OX19+ cells was greater than that of OX8+ cells in the parenchyma and SAS at all stages examined, the distribution of OX19+ cells was almost the same as that of OX8+ cells, OX8+ cells decreased in number before clinical signs subsided, and that after the infiltration of T cells into the parenchyma, cells with dendritic morphology (microglia) expressed Ia antigens in close association with the infiltrating T cells. Adoptive transfer of MBP-sensitized spleen cells provides constant induction of EAE with minimal variation in clinical onset and severity, thus being a useful model for the examination of early events of EAE.