THE SUBARACHNOID SPACE AS A SITE FOR PRECURSOR T-CELL PROLIFERATION AND EFFECTOR T-CELL SELECTION IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

To characterize the phenotype of inflammatory cells in the central ner vous system (CNS) in experimental autoimmune encephalomyelitis (EAE), Lewis rats were immunized with guinea pig myelin basic protein and fro zen sections of the spinal cord with EAE were examined immunohistochem ically using a panel of monoclonal antibodies against T cells and adhe sion molecules. In addition, double immunostaining was performed with glial and T cells markers to examine the interaction between infiltrat ing T cells and reactive brain cells during the course of EAE. In the early stage of EAE, inflammatory cells first appeared in the subarachn oid space (SAS) and infiltrated the subpial region. The majority of in flammatory cells in SAS expressed TCR alpha beta and either CD4 or CD8 molecules. However, only CD4(+) T cells infiltrated the parenchyma wh ile the majority of CD8(+) cells remained in SAS. A similar differenti al localization of T cells was observed with regard to CD45RC molecule s. Inflammatory cells in SAS consisted of both CD45RC(+) and CD45RC(-) population, while those in the parenchyma were largely CD45RC(-). Wit h regard to adhesion molecules, the leptomeninges constitutively expre ssed fibronectin (FN) and intercellular adhesion molecule 1 (ICAM-1). Most SAS inflammatory cells expressed very late activation antigen 4 ( VLA-4) and, to lesser extent, lymphocyte function-associated antigen 1 (LFA-1) in the early stage of EAE. On the other hand, parenchymal inf iltrating cells expressed LFA-1 more strongly in the peak stage. Doubl e staining for V beta 8.2 TCR and microglia demonstrated an increase i n the number of microglia together with morphological changes into rod -shape cells in the vicinity of infiltrating T cells. Furthermore, the se cells expressed adhesion molecules, such as LFA-1, ICAM-1 and CD4. These findings suggest that VLA-4/FN and LFA-1/ICAM-1 interactions bet ween infiltrating cells and brain cells may be involved in the early a nd peak stages of EAE. Phenotype switching occurring in the process of inflammatory cell infiltration may be regulated by these adhesion mol ecules and factor(s) provided by the parenchyma, possibly by microglia .