Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate.

Genain, Claude P.; Nguyen, My-Hoa; Letvin, Norman L.; Pearl, Rachel; Davis, Richard L.; Adelman, Martin H.; Lees, Marjorie B.; Linington, Christopher; Hauser, Stephen L.

doi:10.1172/jci118368

Cited by 298 publications

(196 citation statements)

References 47 publications

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“…The pathogenesis of EAE in common marmosets involves, as in rodents, at least two separate pathogenic pathways. CNS inflammation can be mediated by T cell reactivity to major myelin Ags such as MBP or proteolipid protein (6,7). CNS demyelination, however, requires the involvement of Abs, in particular those directed to MOG (7, 9, 18 -20).…”

Section: Discussionmentioning

confidence: 99%

“…The clinical and pathological expression of myelin-induced EAE in marmosets is thought to result from a synergy of cellular and humoral autoimmune reactivity predominantly directed against two Ags, namely myelin basic protein (MBP) (2,6,7) and myelin/oligodendrocyte glycoprotein (MOG) (7)(8)(9). Hence, for the purpose of the present study, three marmoset twin couples were randomly selected from our colony; one sibling of each twin was immunized with recombinant human MOG (rhMOG), and the other sibling was immunized with purified human MBP (hMBP).…”

mentioning

confidence: 99%

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Myelin/Oligodendrocyte Glycoprotein-Induced Autoimmune Encephalomyelitis in Common Marmosets: The Encephalitogenic T Cell Epitope pMOG24–36 Is Presented by a Monomorphic MHC Class II Molecule

Brok

Uccelli

Rosbo

et al. 2000

The Journal of Immunology

115

130

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Immunization of common marmosets (Callithrix jacchus) with a single dose of human myelin in CFA, without administration of Bordetella pertussis, induces a form of autoimmune encephalomyelitis (EAE) resembling in its clinical and pathological expression multiple sclerosis in humans. The EAE incidence in our outbred marmoset colony is 100%. This study was undertaken to assess the genetic and immunological basis of the high EAE susceptibility. To this end, we determined the separate contributions of immune reactions to myelin/oligodendrocyte glycoprotein (MOG) and myelin basic protein to the EAE induction. Essentially all pathological features of myelin-induced EAE were also found in animals immunized with MOG in CFA, whereas in animals immunized with myelin basic protein in CFA clinical and pathological signs of EAE were lacking. The epitope recognition by anti-MOG Abs and T cells were assessed. Evidence is provided that the initiation of EAE is based on T and B cell activation by the encephalitogenic phMOG14–36 peptide in the context of monomorphic Caja-DRB*W1201 molecules.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Myelin/Oligodendrocyte Glycoprotein-Induced Autoimmune Encephalomyelitis in Common Marmosets: The Encephalitogenic T Cell Epitope pMOG24–36 Is Presented by a Monomorphic MHC Class II Molecule

Brok

Uccelli

Rosbo

et al. 2000

The Journal of Immunology

115

130

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“…by T cells Swanborg, 1995 , but for demyelination the involvement of opsonizing antibodies and complement ap-Ž pears essential Linington and Lassmann, 1987;Linington . et al, 1992;Genain et al, 1995 . T cell autoreactivity may be provoked by major and minor myelin constituents like myelin basic protein, proteolipid protein and myelin oligodendrocyte protein.…”

Section: žmentioning

confidence: 98%

“…jacchus closely resembles MS with respect to clinical presentation, white matter lesion formation in vivo as Ž . assessed by magnetic resonance imaging MRI , and CNS Ž histopathology Genain et al, 1994;McFarland, 1994;Genain et al, 1995;Massacesi et al, 1995;Genain et al, . 1996 .…”

Section: žmentioning

confidence: 99%

Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus)

Laman

Meurs²,

Schellekens³

et al. 1998

Journal of Neuroimmunology

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Ž .Accessory molecules and cytokines are involved in the immunopathogenesis of multiple sclerosis MS and experimental autoimmune Ž . encephalomyelitis EAE in rodent models, and are potential targets for immunotherapy. Evaluation of such experimental therapies requires appropriate animal models. Therefore, we analysed the expression of selected accessory molecules and cytokines in the brain of Ž . marmoset monkeys Callithrix jacchus with acute EAE, a newly described non-human primate model for MS. All animals experienced active disease clinically and histopathologically with strong resemblance to MS. Perivascular infiltrates of mononuclear cells showed abundant expression of CD40. CD40 was expressed on macrophages, indicating that T cell priming and macrophage effector functions Ž . Ž . may result from local CD40-CD40L interactions. CD40 ligand CD40L and B7-2 CD86 were also expressed, but to a lower extent, Ž . while B7-1 CD80 expression was limited. Both pro-inflammatory and anti-inflammatory cytokines were produced within individual Ž . lesions during active disease IFN-a, IFN-g , TNF-a, IL-1a , IL-1b, IL-2, IL-4, IL-10 and IL-12 . This suggests that relative levels rather than sequential expression of Th1-and Th2-type cytokines determine disease activity. These findings demonstrate the value of EAE in marmoset monkeys as a model to assess the role of accessory molecules and cytokines in multiple sclerosis, and to evaluate targeted intervention. q

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“…Antimyelin component antibodies generated under pathological conditions might have either adverse or beneficial effects (van der Veen et al, 1986(van der Veen et al, , 1989Endoh et al, 1986;Sadler et al, 1991;Potter and Stephens, 1994;Genain et al, 1995;Laman et al, 2001;Morris-Downes et al, 2002;Mitsunaga et al, 2002;Schwab, 2004). Moreover, potential pathogenetic roles for antimyelin antibodies, including anti-PLP antibodies, have been suggested in MS (Sun et al, 1991;Warren et al, 1994;Sellebjerg et al, 1995Sellebjerg et al, , 2000Archelos et al, 2000;Carvalho et al, 2003;Berger et al, 2003;Qin et al, 2003;Kanter et al, 2005;Zhang et al, 2005a).…”

Section: Implications For Msmentioning

confidence: 99%

Monoclonal antibodies to distinct regions of human myelin proteolipid protein simultaneously recognize central nervous system myelin and neurons of many vertebrate species

Greenfield¹,

Reddy²,

Lees³

et al. 2006

J of Neuroscience Research

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Myelin proteolipid protein (PLP), the major protein of mammalian CNS myelin, is a member of the proteolipid gene family (pgf). It is an evolutionarily conserved polytopic integral membrane protein and a potential autoantigen in multiple sclerosis (MS). To analyze antibody recognition of PLP epitopes in situ, monoclonal antibodies (mAbs) specific for different regions of human PLP (50–69, 100–123, 139–151, 178–191, 200–219, 264–276) were generated and used to immunostain CNS tissues of representative vertebrates. mAbs to each region recognized whole human PLP on Western blots; the anti‐100–123 mAb did not recognize DM‐20, the PLP isoform that lacks residues 116–150. All of the mAbs stained fixed, permeabilized oligodendrocytes and mammalian and avian CNS tissue myelin. Most of the mAbs also stained amphibian, teleost, and elasmobranch CNS myelin despite greater diversity of their pgf myelin protein sequences. Myelin staining was observed when there was at least 40% identity of the mAb epitope and known pgf myelin proteins of the same or related species. The pgf myelin proteins of teleosts and elasmobranchs lack 116–150; the anti‐100–123 mAb did not stain their myelin. In addition to myelin, the anti‐178–191 mAb stained many neurons in all species; other mAbs stained distinct neuron subpopulations in different species. Neuronal staining was observed when there was at least approximately 30% identity of the PLP mAb epitope and known pgf neuronal proteins of the same or related species. Thus, anti‐human PLP epitope mAbs simultaneously recognize CNS myelin and neurons even without extensive sequence identity. Widespread anti‐PLP mAb recognition of neurons suggests a novel potential pathophysiologic mechanism in MS patients, i.e., that anti‐PLP antibodies associated with demyelination might simultaneously recognize pgf epitopes in neurons, thereby affecting their functions. © 2006 Wiley‐Liss, Inc.

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Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate.

Cited by 298 publications

References 47 publications

Myelin/Oligodendrocyte Glycoprotein-Induced Autoimmune Encephalomyelitis in Common Marmosets: The Encephalitogenic T Cell Epitope pMOG24–36 Is Presented by a Monomorphic MHC Class II Molecule

Myelin/Oligodendrocyte Glycoprotein-Induced Autoimmune Encephalomyelitis in Common Marmosets: The Encephalitogenic T Cell Epitope pMOG24–36 Is Presented by a Monomorphic MHC Class II Molecule

Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus)

Monoclonal antibodies to distinct regions of human myelin proteolipid protein simultaneously recognize central nervous system myelin and neurons of many vertebrate species

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