Macrophages in T cell line-mediated, demyelinating, and chronic relapsing experimental autoimmune encephalomyelitis in Lewis rats.
About 50% of the mononuclear cells in the perivascular lesions in the central nervous system (CNS) of rats suffering from experimental allergic encephalomyelitis (EAE) are blood-borne macrophages. In this study we investigated the role of these macrophages in different variants of EAE, using a liposome-mediated macrophage depletion technique. Intravenously injected liposomes containing dichloromethylene diphosphonate (Cl2MDP) are ingested by macrophages and cause temporary and selective elimination of these cells. Macrophage depletion during EAE induced by a T cell line specific for myelin basic protein (MBP; T cell-EAE) suppresses development of neurological signs of EAE. T cell-EAE with pronounced demyelination as induced by an additionally injected MoAb directed against myelin oligodendrocyte glycoprotein (MOG) was also significantly ameliorated after macrophage depletion. During chronic relapsing EAE (CR-EAE) the occurrence of relapses was prevented or suppressed, provided that the liposomes were injected before the initiation of a putative relapse. A chronic progressive course of CR-EAE was not modified by Cl2MDP containing liposome treatment. Histologic examination of the CNS of liposome-treated animals confirmed decreased infiltration of macrophages into the parenchyma in the rats with T cell and AD-EAE, whereas T cells were still present.
Huitinga
I
I
Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
Ruuls
S R
SR
Jung
S
S
Van Rooijen
N
N
Hartung
H P
HP
Dijkstra
C D
CD
D000818:Animals; D004002:Clodronic Acid / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D003711:Demyelinating Diseases / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology
D004002:Clodronic Acid; D016572:Cyclosporine