Acute experimental allergic encephalomyelitis in the mouse: Immunopathology of the developing lesion

Abstract

To investigate the sequence of immunopathologic events during lesion formation in acute experimental allergic encephalomyelitis (EAE), SJL/J mice were inoculated with isogeneic spinal cord in complete Freund's adjuvant (CFA) and with Bordetella pertussis on Days 1 and 3 postinoculation (PI). Mice were sampled at different time points PI and T cells, T-cell subsets, Ia + cells, Ig + cells, albumin, and Ig deposits were localized in frozen sections by the avidinbiotin complex (ABC) method and direct fluorescence. Furthermore, samples were stained for Ia antigen, myelin basic protein (MBP), and galactocerebroside (GC) localization on endothelial cells by the ABC technique. Clinical and pathologic observations were correlated with the immunopathologic results. It was found that early in the disease process myelin and Ia-antigens were demonstrable on endothelial cells within the central nervous system (CNS). Simultaneously, damage to the blood-brain barrier was apparent, as indicated by albumin deposits, and small numbers of infiltrating T cells, T-cell subsets, and Ia + cells were found. With time PI, the density of infiltrating total T cells (Thy-1.2 +), helper/inducer (Lyt-1 +), and suppressor/cytotoxic (Lyt-2 +) T cells increased; Lyt-1 + and Lyt-2 + cells were detectable in meningeal as well as parenchymal infiltrates, while later on, Lyt-1 + cells showed some predilection for the CNS parenchyma and Lyt-2 + cells for meninges. Ia + cells (B cells, macrophages, activated T cells) were present in small numbers only. Ig + cells (B cells and macrophages) appeared shortly before onset of signs and persisted in moderate numbers. These results reconfirm the importance of early T-cell involvement for the development of EAE; they might also indicate a secondary role for Ig + cells and are consistent with the concept that presentation of myelin antigens to T cells might occur locally on Ia-bearing endothelial cells within the CNS.