Induction of MHC Class I Genes in Neurons

Neumann, Harald; Cavalié, Adolfo; Jenne, Dieter E.; Wekerle, Hartmut

doi:10.1126/science.7624779

Cited by 414 publications

(278 citation statements)

References 9 publications

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“…It has been hypothesized that there is a suppressed inducibility of MHC in functionally active neurons but with eg, viral damage, loss of bioelectric activity of cells could up-regulate MHC molecules for recognition by T cells and thus clearance of abnormal cells. 38 Whether differentiation of muscle fibers, with the expression of MHC on the fiber membrane, contributes to activation or to development of anergy in T lymphocytes is probably dependent on presence of classical co-stimulatory molecules. Such molecules are those within the B7 family, and these have not been demonstrated on muscle fibers to date.…”

Section: Discussionmentioning

confidence: 99%

Skeletal Muscle Fibers Express Major Histocompatibility Complex Class II Antigens Independently of Inflammatory Infiltrates in Inflammatory Myopathies

Englund

Lindroos

Nennesmo

et al. 2001

The American Journal of Pathology

130

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The aim of our study was to address the question of whether muscle fibers express major histocompatibility complex (MHC) class II in inflammatory myopathies. For this purpose we performed a systematic study of MHC class II antigen expression on muscle fiber membranes in muscle tissue from polymyositis and dermatomyositis patients in various stages of disease activity. Thirty-two patients with classical clinical signs of myositis were divided into subgroups depending on duration of clinical signs of myositis and presence or absence of inflammatory infiltrates in muscle tissue. Immunohistochemistry as well as double-immunofluorescence stainings were used to identify the presence of MHC class II in muscle tissue. MHC class I was included for comparison. Quantification of positive staining was performed using an image analysis system in addition to evaluation by manual microscopic scoring and laser confocal microscopy. It was demonstrated that a significant proportion of skeletal muscle fibers in inflammatory myopathies express MHC class II as well as MHC class I and that MHC antigen expression is independent of the inflammatory cell infiltration. Furthermore, there were no differences in staining pattern between polymyositis and dermatomyositis patients. Our results indicate that MHC class II and MHC class I molecules may be involved in initiating and maintaining the pathological condition in myositis rather than only being a consequence of a preceding local inflammation.

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Section: Discussionmentioning

confidence: 99%

Skeletal Muscle Fibers Express Major Histocompatibility Complex Class II Antigens Independently of Inflammatory Infiltrates in Inflammatory Myopathies

Englund

Lindroos

Nennesmo

et al. 2001

The American Journal of Pathology

130

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“…Hippocampal neurons were prepared from embryonic day 18 Wistar rats as described 17 and cultured in DMEM/10% FCS for 24 h. The medium was then replaced with DMEM/B27 supplement (Invitrogen). For the generation of PC12 cells stably expressing DISC1, FLAG-tagged human DISC1 cDNA in pcDNA3.1( þ ) was linearized by ScaI and transfected to PC12 cells.…”

Section: Plasmidsmentioning

confidence: 99%

Disrupted-In-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth

et al. 2003

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Disrupted-In-Schizophrenia 1 (DISC1) was identified as a novel gene disrupted by a (1;11)(q42.1;q14.3) translocation that segregated with schizophrenia in a Scottish family. Predicted DISC1 product has no significant homology to other known proteins. Here, we demonstrated the existence of DISC1 protein and identified fasciculation and elongation protein zeta-1 (FEZ1) as an interacting partner of DISC1 by a yeast two-hybrid study. FEZ1 and its nematode homolog are reported to represent a new protein family involved in axonal outgrowth and fasciculation. In cultured hippocampal neurons, DISC1 and FEZ1 colocalized in growth cones. Interactions of these proteins were associated with F-actin. In the course of neuronal differentiation of PC12 cells, upregulation of DISC1/FEZ1 interaction was observed as along with enhanced extension of neurites by overexpression of DISC1. The present study shows that DISC1 participates in neurite outgrowth through its interaction with FEZ1. Recent studies have provided reliable evidence that schizophrenia is a neurodevelopmental disorder. As there is a high level of DISC1 expression in developing rat brain, dysfunction of DISC1 may confer susceptibility to psychiatric illnesses through abnormal development of the nervous system.

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“…Oligodendrocytes express MHC class I, and its expression is increased in MS (Hoftberger et al, 2004); therefore, myelin-derived self epitopes on the surface of oligodendrocytes constitute one possible target for CD8 + T cells within the CNS, and studies have reported that myelin-specific CD8 + T cells can trigger the death of cultured human oligodendrocytes (Ruijs et al, 1993;Jurewicz et al, 1998). At first blush, neurons appear less likely targets for direct CD8 + T cell effects, because they express very low levels of MHC class I, and of other components of the class I antigen presentation pathway (Joly et al, 1991;Joly and Oldstone, 1992); however, MHC class I is up-regulated by neurons in response to injury or inflammation (Neumann et al, 1995;Neumann et al, 1997), potentially rendering them vulnerable to CD8 + T cell-mediated cytotoxicity. Indeed, blood-donor derived CD8 + cells can cause axon transection in cultured neurons (Medana et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Myelin oligodendrocyte glycoprotein peptide-induced experimental allergic encephalomyelitis and T cell responses are unaffected by immunoproteasome deficiency

Frausto

Crocker

Eam

et al. 2007

Journal of Neuroimmunology

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The inoculation of MOG peptides into C57BL/6 mice induces CD4 + and CD8 + T cells, and recent work has shown that adoptive transfer of the latter population, after extensive in vitro stimulation, can cause EAE in naïve recipient mice. Herein, we have evaluated the incidence and severity of EAE, and the induction of CD4 + and CD8 + T cells, following MOG peptide inoculation of wt mice and of LMP-2KO mice that lack an intact immunoproteasome, a cytoplasmic organelle that is induced by chronic inflammation and that may be important for the presentation of MHC class I epitopes to CD8 + T cells. We report that EAE, evaluated by both clinical and histological criteria, is similar in LMP-2KO mice and wildtype C57B/6 mice (wt) in response to immunization with MOG peptides MOG 35-55 and MOG [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] , suggesting that the immunoproteasome does not play a key role in the development of demyelinating disease. Furthermore, and consistent with previous reports, peptidespecific CD8 + T cells were barely detectable in the CNS of peptide-immunized mice, although peptide-specific CD4 + T cells were abundant. Therefore, we used a new technique to look for autoreactive CD8 + T cells in MOG peptide-immunized mice, and we report the identification of CD4 + and CD8 + T cells that, as late as 19 days after peptide injection, are actively producing IFNγ in vivo, in response to in vivo antigen contact.

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Induction of MHC Class I Genes in Neurons

Cited by 414 publications

References 9 publications

Skeletal Muscle Fibers Express Major Histocompatibility Complex Class II Antigens Independently of Inflammatory Infiltrates in Inflammatory Myopathies

Skeletal Muscle Fibers Express Major Histocompatibility Complex Class II Antigens Independently of Inflammatory Infiltrates in Inflammatory Myopathies

Disrupted-In-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth

Myelin oligodendrocyte glycoprotein peptide-induced experimental allergic encephalomyelitis and T cell responses are unaffected by immunoproteasome deficiency

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