Macrophages in T cell line-mediated, demyelinating, and chronic relapsing experimental autoimmune encephalomyelitis in Lewis rats

Abstract

SUMMARYAbout 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 (CI2MDP) 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 myeiin 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 myeiin 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 CI2MDP 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.

Modulation of Macrophage Infiltration and Inflammatory Activity by the Phosphatase SHP-1 in Virus-Induced Demyelinating Disease

“…Thus, the results of the present study are relevant to CNS inflammatory diseases in which either adaptive or innate immune responses play an important role but in which macrophages constitute the main effectors of tissue destruction. Indeed, infiltrating macrophages have been demonstrated previously to be essential effectors of demyelination in both the TMEV (7,25,86,88) and the experimental autoimmune encephalomyelitis (26,48,49,101) mouse models of MS. Also, while the role of T cells in disease pathogenesis may or may not be a predominant feature of demyelinating lesions in both humans with MS and animal models, the importance of macrophages as essential effectors of demyelination and paralysis is now well-established. Previous TMEV studies have shown that the extent of CNS macrophage infiltration correlates with disease severity (58,88).…”

Multiple Sclerosis: Myeloperoxidase Immunoradiology Improves Detection of Acute and Chronic Disease in Experimental Model

“…Demyelination and axonal damage, however, are more likely caused by innate immune cells such as monocytes, macrophages, and neutrophils (2). Accordingly, in experimental autoimmune encephalomyelitis (EAE), the most commonly used experimental model of MS, depletion or inactivation of monocytes (3,4), microglia (5), and neutrophils (6) effectively suppresses disease.…”

Characterization of relapsing–remitting and chronic forms of experimental autoimmune encephalomyelitis in C57BL/6 mice

“…EAE can be induced in several species by immunization with myelin antigens or via adoptive transfer of myelin-reactive T cells. EAE can be initiated by CD4 1 or CD8 1 T cells (Huseby et al, 2001;Mokhtarian et al, 1984;Pettinelli and McFarlin, 1981;Sun et al, 2001), and macrophages/ microglia play an important role in disease progression (Bauer et al, 1995;Heppner et al, 2005;Huitinga et al, 1990Huitinga et al, , 1995Tran et al, 1998). Chemokines and cytokines, including MCP-1/CCL2, MIP-1a/CCL3, tumor necrosis factor alpha (TNF-a), and interleukin-17 , are implicated in the pathogenesis of EAE Imitola et al, 2005;Iwakura and Ishigame, 2006;Karpus and Kennedy, 1997).…”