Screening of several H-2 congenic mouse strains identified H-2q mice as highly susceptible to MOG-induced EAE with minimal adjuvant requirement

Abdul-Majid, Khairul-Bariah; Jirholt, Johan; Stadelmann, Christine; Stefferl, Andreas; Kjellén, Peter; Wallström, Erik; Holmdahl, Rikard; Lassmann, Hans; Olsson, Tomas; Harris, Robert A.

doi:10.1016/s0165-5728(00)00360-x

Cited by 63 publications

(57 citation statements)

References 47 publications

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“…A role for B cells in the pathogenesis of EAE has recently been demonstrated in DBA/1 mice immunized with MOG (6,8). These animals experienced an extensive demyelination in the CNS during EAE progression that was shown to be dependent on the presence of B cells and the production of autoreactive Abs.…”

Section: Discussionmentioning

confidence: 98%

“…It is generally considered that CD4 ϩ T cells initiate EAE (4), and Th1-associated proinflammatory cytokines such as IFN-␥ and TNF-␣ are important disease-promoting cytokines (5). We have recently developed a pertussis toxin-free MOG-induced EAE model in DBA/1 mice that shares the salient pathological features of human MS, namely involvement of both CD4 ϩ and CD8 ϩ T cells, B cells (6), and Fc␥R (7), and that is characterized by multiple demyelinated lesions in the CNS (8).…”

Section: E Xperimental Autoimmune Encephalomyelitis (Eae)mentioning

confidence: 99%

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Expression of the Long Form of Human FLIP by Retroviral Gene Transfer of Hemopoietic Stem Cells Exacerbates Experimental Autoimmune Encephalomyelitis

Djerbi

Abdul-Majid

Abedi‐Valugerdi

et al. 2003

The Journal of Immunology

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Subsidence of inflammation and clinical recovery in experimental autoimmune encephalomyelitis (EAE) is postulated to involve apoptosis of inflammatory cells. To test this concept, we examined the effects of overexpressing the long form of human FLICE-inhibitory protein, a potent inhibitor of death receptor-mediated apoptosis, in myelin oligodendrocyte glycoprotein-induced EAE in DBA/1 mice. We found that overexpression of the long form of human FLICE-inhibitory protein by retroviral gene transfer of hemopoietic stem cells led to a clinically more severe EAE in these mice compared with control mice receiving the retroviral vector alone. The exacerbated disease was evident by an enhanced and prolonged inflammatory reaction in the CNS of these animals compared with control mice. The acute phase of EAE was characterized by a massive infiltration of macrophages and granulocytes and a simultaneous increase in TNF-α production in the CNS. In the chronic phase of the disease, there was a prolonged inflammatory response in the form of persistent CD4+ T and B cells in the CNS and a peripheral Th1 cytokine bias caused by elevated levels of IFN-γ and reduced levels of IL-4 in the spleen. Our findings demonstrate that death receptor-mediated apoptosis can be important in the pathogenesis of EAE and further emphasize the need for effective apoptotic elimination of inflammatory cells to achieve disease remission.

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Section: Discussionmentioning

confidence: 98%

Section: E Xperimental Autoimmune Encephalomyelitis (Eae)mentioning

confidence: 99%

Expression of the Long Form of Human FLIP by Retroviral Gene Transfer of Hemopoietic Stem Cells Exacerbates Experimental Autoimmune Encephalomyelitis

Djerbi

Abdul-Majid

Abedi‐Valugerdi

et al. 2003

The Journal of Immunology

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“…EAE was induced by active immunization, and disease severity was assessed by assigning clinical scores following published protocols (52,53). In brief, 8-to 10-wk-old female mice were immunized at the base of the tail and in both thighs with 200 μg of mouse MOG peptide (custom synthesized by GenScript USA) emulsified in CFA (Difco Laboratories) that had been supplemented with Mycobacterium tuberculosis strain H37Ra to 4 mg/mL.…”

Section: Methodsmentioning

confidence: 99%

CD318 is a ligand for CD6

Enyindah-Asonye

Ruth

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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It has been proposed that CD6, an important regulator of T cells, functions by interacting with its currently identified ligand, CD166, but studies performed during the treatment of autoimmune conditions suggest that the CD6-CD166 interaction might not account for important functions of CD6 in autoimmune diseases. The antigen recognized by mAb 3A11 has been proposed as a new CD6 ligand distinct from CD166, yet the identity of it is hitherto unknown. We have identified this CD6 ligand as CD318, a cell surface protein previously found to be present on various epithelial cells and many tumor cells. We found that, like CD6 knockout (KO) mice, CD318 KO mice are also protected in experimental autoimmune encephalomyelitis. In humans, we found that CD318 is highly expressed in synovial tissues and participates in CD6-dependent adhesion of T cells to synovial fibroblasts. In addition, soluble CD318 is chemoattractive to T cells and levels of soluble CD318 are selectively and significantly elevated in the synovial fluid from patients with rheumatoid arthritis and juvenile inflammatory arthritis. These results establish CD318 as a ligand of CD6 and a potential target for the diagnosis and treatment of autoimmune diseases such as multiple sclerosis and inflammatory arthritis.C D6 is a marker of T cells and an important T-cell regulator (1). Recent genome-wide association studies also identified CD6 as a risk gene for multiple sclerosis (MS) (2-5), an autoimmune disease in which T cells play a vital role in the pathogenesis. CD6 is composed of three extracellular domains (domains 1, 2, and 3), and it functions by interacting with its ligand(s) (6). The domain 3 of CD6 has been shown to be the site that the identified CD6 ligand, CD166, also known as ALCAM (activated leukocyte cell adhesion molecule), binds to (7). However, anti-CD166 antibodies only partially blocked the binding of thymic epithelial cells to CD6-overexpressing COS cells, and mAbs blocking CD6-CD166 interactions do not abolish CD6 function (8, 9). Itolizumab, an anti-CD6 mAb developed in Cuba and approved in India for treating psoriasis, reduces pathogenic T-cell responses in patients with psoriasis, but this mAb binds to domain 1 of CD6 instead of domain 3, and it does not interfere with the CD6-CD166 interaction. Interestingly, UMCD6, a mouse antihuman CD6 mAb that we found highly effective in treating encephalomyelitis (EAE) in CD6 humanized mice, also fails to block the CD6-CD166 interaction. All these studies suggest the existence of an additional CD6 ligand, other than CD166, that binds to domain 1 of CD6, and could be critical for CD6 function in autoimmune conditions. Further studies using a CD6 fusion protein as a bait to pull down CD6-binding proteins from synovial fibroblast surface proteins showed the binding of three polypeptides (10). One of these polypeptides was identified as CD166, and the identities of the other two were unknown (11). A mAb termed 3A11 was developed, and the antigen recognized by this mAb was identified as the new ligand of ...

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“…We produced rMOG (rat MOG ) protein in Escherichia coli as described 28 . MOG peptides 35-55, 79-90, 97-114 (rat sequences) and MBP Ac1-11 (mouse sequence) were synthesized by Genemed, and MBP Ac1-11Met4Lys8 was synthesized at the California Institute of Technology, using Fmoc/HBTU chemistry.…”

Section: Proteins and Peptidesmentioning

confidence: 99%

Differential regulation of central nervous system autoimmunity by TH1 and TH17 cells

Stromnes¹,

Cerretti²,

Liggitt

et al. 2008

Nat Med

558

498

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Multiple sclerosis is an inflammatory, demyelinating disease of the central nervous system (CNS) characterized by a wide range of clinical signs 1 . The location of lesions in the CNS is variable and is a crucial determinant of clinical outcome. Multiple sclerosis is believed to be mediated by myelinspecific T cells, but the mechanisms that determine where T cells initiate inflammation are unknown. Differences in lesion distribution have been linked to the HLA complex, suggesting that T cell specificity influences sites of inflammation2. We demonstrate that T cells that are specific for different myelin epitopes generate populations characterized by different T helper type 17 (T H 17) to T helper type 1 (T H 1) ratios depending on the functional avidity of interactions between TCR and peptide-MHC complexes. Notably, the T H 17:T H 1 ratio of infiltrating T cells determines where inflammation occurs in the CNS. Myelin-specific T cells infiltrate the meninges throughout the CNS, regardless of the T H 17:T H 1 ratio. However, T cell infiltration and inflammation in the brain parenchyma occurs only when T H 17 cells outnumber T H 1 cells and trigger a disproportionate increase in interleukin-17 expression in the brain. In contrast, T cells showing a wide range of T H 17:T H 1 ratios induce spinal cord parenchymal inflammation. These findings reveal critical differences in the regulation of inflammation in the brain and spinal cord.Experimental autoimmune encephalomyelitis (EAE) is an animal model that shows many similarities to multiple sclerosis3. However, rodent EAE differs from multiple sclerosis by manifesting as ascending flaccid paralysis, reflecting unexplained preferential targeting of inflammation to the spinal cord (described as classic EAE). In a small number of antigenspecific models, brain inflammation occurs (described as atypical EAE)4 -8. Interferon-γ (IFN-γ) deficiency also causes certain myelin-specific T cells to preferentially induce brain

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Screening of several H-2 congenic mouse strains identified H-2q mice as highly susceptible to MOG-induced EAE with minimal adjuvant requirement

Cited by 63 publications

References 47 publications

Expression of the Long Form of Human FLIP by Retroviral Gene Transfer of Hemopoietic Stem Cells Exacerbates Experimental Autoimmune Encephalomyelitis

Expression of the Long Form of Human FLIP by Retroviral Gene Transfer of Hemopoietic Stem Cells Exacerbates Experimental Autoimmune Encephalomyelitis

CD318 is a ligand for CD6

Differential regulation of central nervous system autoimmunity by TH1 and TH17 cells

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