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 nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE), Lewis rats were immunized with guinea pig myelin basic protein and frozen sections of the spinal cord with EAE were examined immunohistochemically using a panel of monoclonal antibodies against T cells and adhesion molecules. In addition, double immunostaining was performed with glial and T cells markers to examine the interaction between infiltrating T cells and reactive brain cells during the course of EAE. In the early stage of EAE, inflammatory cells first appeared in the subarachnoid space (SAS) and infiltrated the subpial region. The majority of inflammatory cells in SAS expressed TCR alpha beta and either CD4 or CD8 molecules. However, only CD4+ T cells infiltrated the parenchyma while the majority of CD8+ cells remained in SAS. A similar differential localization of T cells was observed with regard to CD45RC molecules. Inflammatory cells in SAS consisted of both CD45RC+ and CD45RC- population, while those in the parenchyma were largely CD45RC-. With regard to adhesion molecules, the leptomeninges constitutively expressed 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 infiltrating cells expressed LFA-1 more strongly in the peak stage. Double staining for V beta 8.2 TCR and microglia demonstrated an increase in the number of microglia together with morphological changes into rod-shape cells in the vicinity of infiltrating T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Shin
T
T
Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Japan.
Kojima
T
T
Tanuma
N
N
Ishihara
Y
Y
Matsumoto
Y
Y
D000818:Animals; D002450:Cell Communication; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D005353:Fibronectins / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008297:Male; D017628:Microglia / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D016029:Receptors, Very Late Antigen / Q000032:analysis; D013346:Subarachnoid Space / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D005353:Fibronectins; D016169:Lymphocyte Function-Associated Antigen-1; D016029:Receptors, Very Late Antigen