Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The repertoire of TCR V beta genes transcribed and expressed within the central nervous system was determined in mice with experimental allergic encephalomyelitis. Disease was induced in (PL/J x SJL/)F1 mice by immunizing with myelin basic protein-acetylated peptide 1-11, and mice were sacrificed at intervals from day 3 postimmunization to 3 wk after recovery from disease. Transcription of V beta genes was determined by reverse transcriptase polymerase chain reaction on RNA extracted from spinal cord, and expression of the V beta gene products was detected by immunohistochemistry with mAb specific for various V beta proteins. Multiple V beta genes were found to be transcribed and expressed in the central nervous system starting 7 days after immunization, and continuing up to 3 wk after clinical recovery. Preferential utilization of a single TCR V beta gene was not detected in the central nervous system at any time in the course of disease.
 ...
PMID:Diverse T cell receptor V beta gene usage in the central nervous system in experimental allergic encephalomyelitis. 847 51

The pathogenic role of myelin basic protein (MBP)-specific T lymphocytes in multiple sclerosis (MS) has been suggested by the encephalitogenicity of MBP-specific T cells in experimental allergic encephalomyelitis (EAE). In humans, extensive analysis of TCRs involved in MBP recognition has led to conflicting results, varying from an intra- and/or interindividual restriction to high diversity in TCRAV/TCRBV gene usage. We previously established MBP-specific T cell lines (TCLs) from healthy monozygous twins and characterized their fine epitope specificity. In this study, we report on the TCR alpha beta gene usage of 52 of these MBP TCLs that are specific for epitopes recognized by both co-twins within the same pair. High overall diversity in the TCR alpha and TCR beta genes used for recognition of this self-Ag, MBP, was observed. Variable genes belonging to 19 different TCRAV and 16 different TCRBV subfamilies are expressed by the 52 TCLs herein studied. In co-twins, TCLs utilized genes belonging to common TCRAV and/or TCRBV gene subfamilies in 7 of 13 instances of shared epitope recognition. Statistical analysis of intrapair concordance for TCR gene usage for the recognition of a given peptide did not show any significant deviation from values that would be anticipated in the absence of genetic background effect.
 ...
PMID:TCR alpha beta gene usage for myelin basic protein recognition in healthy monozygous twins. 862 10

Theiler's murine encephalomyelitis viruses (TMEVs) are endemic enteric pathogens of mice that cause immune-mediated, chronic, progressive, central nervous system (CNS) demyelinating disease in susceptible strains. Analysis of T cell phenotype and functional state from TMEV-infected SJL/J mice by flow cytometry reveals that 13.5 to 25% of the CD4+ T cells in the CNS express high affinity IL-2R, a marker of recent T cell activation, whereas splenic levels of CD4+IL-2R+ T cells generally range between 2 and 8.5%. In contrast, very few CD8+ T cells (<1-2%) from either site express IL-2R. From days 20 to 119 postinfection, the percentage of CD4+IL-2R+ T cells increases gradually in the CNS, but varies little in the spleen. CD4+ T cells isolated from the spinal cord of infected mice proliferate in vitro in response to viral Ag. Similar T cell phenotypes were found in experimental autoimmune encephalomyelitis, an established model of CD4+ T cell-mediated demyelination. In addition, most CD4+ and CD8+ T cells in CNS isolates from TMEV-infected mice are CD44+, indicating that prior activation may be required to traffic through and/or be retained in the CNS. Finally, TCR V beta region usage as well as IL-2R expression by individual V beta region subsets are heterogeneous in both the CNS and spleen. These results are consistent with a model in which a polyclonal population of TMEV-specific, CD4+ Th1 cells plays a major effector role in the demyelinating process.
 ...
PMID:Flow cytometric and functional analyses of central nervous system-infiltrating cells in SJL/J mice with Theiler's virus-induced demyelinating disease. Evidence for a CD4+ T cell-mediated pathology. 862 48

Regulatory T cells recognizing TCR determinants presumably play a critical role in the control of experimental autoimmune encephalomyelitis, a prototype tissue-specific autoimmune disease. This study was initiated to determine whether regulatory T cells can be induced against a V beta 17a CDR2 peptide (residues 50-68) in SJL/J mice. Although the TCR peptide showed regulatory effects in vivo, the presence of T cells specific for the peptide could not be proven with conventional proliferation assays. Unexpectedly, in the presence of myelin basic protein-specific T clone cells (Tcc), the sensitized spleen cells vigorously proliferated in response to the TCR peptide. The subsequent experiment showed that this was due to the outstanding capability of the Tcc as APC for the exogenous TCR peptide. Using the Tcc as APC, we were able to establish V beta 17a50-68-specific T cell lines from in vivo primed spleen cells. The line cells were MHC class I restricted and dominated by T cells with a distinct surface phenotype (CD4-CD8-V beta 17a+). Presentation of the peptide by the Tcc was inhibited by treatment with gelonin that could block a MHC class I presentation pathway. The ability of T cells to present the TCR peptide was not related to their Ag specificity, but correlated with the expression levels of MHC class I molecules and adhesion molecules such as intercellular adhesion molecule-1 and B7-1 on their surface. The TCR peptide-specific T cells produced a soluble mediator(s) that is inhibitory for T cell activation and were protective against actively induced experimental autoimmune encephalomyelitis. These results show that V beta 17a50-68 vaccination induces regulatory CD4-CD8- T cells that could interact with T cells presenting relevant TCR fragments.
 ...
PMID:T-T cellular interaction between CD4-CD8- regulatory T cells and T cell clones presenting TCR peptide. Its implication for TCR vaccination against experimental autoimmune encephalomyelitis. 875 68

In the present study we address the question of whether distinct self-determinants can target alternative autoimmune disease patterns in experimental autoimmune encephalomyelitis (EAE), an animal model widely used for studying multiple sclerosis. We have found that the clinical course of EAE can be determined by the target peptide selected for induction of disease. In SJL/J mice, actively induced and passively transferred EAE mediated by the immunodominant PLP determinants p139-151 and p178-191 consistently produced a rapid onset of severe clinical signs. In contrast, a delayed onset of both active and passive EAE is associated with the nondominant cryptic PLP determinant p104-117. The delayed disease induced with p104-117 is not associated with any unusual peptide feature, with bystander immunoregulation, with inept class II MHC binding, or with failure to induce T cell expression of CD44, VLA-4, or IL-2 receptor upon activation. However, delayed disease is associated with innate qualities of the T cell repertoire responding to the p104-117 determinant. T cell lines responding to the cryptic p104-117 show limited TCR-V beta utilization compared to the diverse repertoire responding to the dominant p139-151 determinant. The repertoire deletions are accompanied by low level production of pathogenic Th1 cytokines (IFN gamma; IL-2) and increased production of regulatory Th2 (IL-4) cytokine in activated p104-117 primed T cells. Thus, the delayed encephalitogenicity of p104-117 may be due to TCR-V beta deletions and activation defects in the responding T cell repertoire. The development of "slow disease" mediated by autoreactivity against hidden self-determinants may have important implications in the pathogenesis of both relapsing and chronic autoimmune demyelinating disease.
 ...
PMID:Determinant-regulated onset of experimental autoimmune encephalomyelitis: distinct epitopes of myelin proteolipid protein mediate either acute or delayed disease in SJL/J mice. 882 78

To study T cell apoptosis during spontaneous recovery from experimental autoimmune encephalomyelitis (EAE), we extracted lymphocytes from the spinal cords of Lewis rats with EAE induced by inoculation with myelin basic protein (MBP) and adjuvants. Using flow cytometry we assessed the numbers of CD5+ and TCR alpha beta + lymphocytes, as well as V beta 8.2+ lymphocytes, which constitute the predominant encephalitogenic MBP-reactive cells in Lewis rats. Rats developed neurological signs of disease 10-12 days after inoculation. The peak of disease was on day 14 after inoculation and was followed by clinical recovery. The numbers of CD5+, TCR alpha beta + and V beta 8.2+ cells obtained from the spinal cord were greatest on day 13. During spontaneous clinical recovery, there was a decline in the numbers of all the cells studied, with a selective loss of V beta 8.2+ cells from the CD5+ and TCR alpha beta + populations. To determine whether the decline in lymphocyte numbers was due to apoptosis, we used simultaneous surface labelling and propidium iodide staining of the DNA of the cells extracted from the spinal cord. From day 14 onwards, there was selective enrichment of V beta 8.2+ cells in the apoptotic population, and the percentage of V beta 8.2+ cells undergoing apoptosis was greater than the percentages of CD5+ and TCR alpha beta + cells undergoing apoptosis. These findings indicate that recovery from acute EAE is associated with the selective apoptosis, in the central nervous system, of these disease-relevant cells. The findings in this study of actively induced EAE are similar to those of our previous study of EAE induced by transfer of encephalitogenic MBP-specific T cells (Z. Tabi et al., Eur. J. Immunol. 24: 2609-2617, 1994) and further support the hypothesis that selective apoptosis of autoreactive T cells in the central nervous system is of primary importance in spontaneous recovery from EAE.
 ...
PMID:Apoptosis of V beta 8.2+ T lymphocytes in the spinal cord during recovery from experimental autoimmune encephalomyelitis induced in Lewis rats by inoculation with myelin basic protein. 883 65

Early studies of murine experimental autoimmune encephalomyelitis (EAE) induced with myelin basic protein (MBP) divide various mouse strains into either "susceptible" or "resistant" phenotypes. Resistance is defined as lack of encephalitogenic responses after active immunization or adoptive transfer. It is now becoming clear that this unresponsiveness is not due to the inability of T cells to recognize MBP in the context of major histocompatibility complex (MHC) gene products. Using various manipulations, many laboratories are able to induce severe EAE in these strains. We previously reported that a combination of adoptive transfer and subsequent challenge of the recipients with MBP could overcome the resistance in many mouse strains (Shaw et al.: J Neuroimmunol 39:139-150, 1992). This approach now enables us to identify the encephalitogenic epitope and T cell receptor V beta usage in a prototype strain, C57BL/6 (B6). Pepsin-digested MBP fragments first located a major T cell epitope in a polypeptide containing residues 44-88. Overlapping synthetic peptides narrowed this epitope to p60-80. Truncated peptides from the carboxyl- or amino-terminus further mapped a minimal peptide to p67-76. This encephalitogenic epitope appears to be unique to B6 mice. Independent encephalitogenic T cell clones specific for this epitope were also generated. Of six such clones analyzed, five different TCR V beta's were found. Whether unbiased usage of encephalitogenic TCR V beta gene segments in B6 mice is related to its EAE resistant phenotype is not clear at this point.
 ...
PMID:Induction of myelin basic protein-specific experimental autoimmune encephalomyelitis in C57BL/6 mice: mapping of T cell epitopes and T cell receptor V beta gene segment usage. 889 80

Previous studies of experimental allergic encephalomyelitis (EAE) in the LER rat have suggested that amino acid differences present in the LER TCR V beta 8.2 chain may be associated with disease resistance. We report here that LEW rats bred to express a V beta 8.2 gene from DA rats, identical to that found in LER, are susceptible to EAE induction. Furthermore, T cells infiltrating the spinal cord of diseased animals primarily utilized V beta 8.2 and the associated AspSer CDR3 motif, typical of TCR V beta 8.2 chains expressed by pathogenic, anti-MBP responsive T cells in the LEW rat.
 ...
PMID:Analysis of T cell receptor beta chains in the rat: I. Allelic polymorphism of V beta 8.2 is not a predisposing genetic factor in susceptibility to experimental allergic encephalomyelitis. 889 81

We have studied the effects of corticosteroid treatment on the numbers of lymphocytes obtained from the spinal cords of Lewis rats with acute experimental autoimmune encephalomyelitis (EAE) induced by inoculation with myelin basic protein (MBP) and adjuvants. Flow cytometric studies showed that treatment with dexamethasone (4 mg/kg) 8-12 h prior to study on day 14 after inoculation resulted in a reduction in the numbers of CD5+, TCR alpha beta + and V beta 8.2+ cells in the spinal cord. Limiting dilution analysis indicated that dexamethasone treatment 12 h prior to study on day 12 after inoculation reduced the frequencies of MBP-reactive and interleukin-2-responsive lymphocytes in the spinal cord to low levels, but reduced the frequency of concanavalin-A-responsive lymphocytes to a lesser extent. Using propidium iodide staining of nuclear chromatin we also studied lymphocyte apoptosis. Greater numbers of apoptotic cells were found in the cells extracted from the spinal cords of rats, examined on day 14, that had been treated 1-12 h previously with dexamethasone, than in saline-treated controls. This increased level of apoptosis was observed in the CD5+ and TCR alpha beta + cell populations. At 1-4 h after dexamethasone treatment there was a reduction in the selective apoptosis of V beta 8.2+ cells that normally occurs during spontaneous recovery from EAE. Therefore apoptosis of V beta 8.2+ cells cannot explain the reduction in the numbers of V beta 8.2+ cells and MBP-reactive cells in the CNS after dexamethasone treatment. By 8-12 h after dexamethasone treatment the selectivity of the apoptotic process was restored. These studies suggest that a reduction in the number of T-lymphocytes in the central nervous system contributes to the beneficial effects of corticosteroids in EAE.
 ...
PMID:Corticosteroid treatment of experimental autoimmune encephalomyelitis in the Lewis rat results in loss of V beta 8.2+ and myelin basic protein-reactive cells from the spinal cord, with increased total T-cell apoptosis but reduced apoptosis of V beta 8.2+ cells. 889 17

The nature of the autoimmune T cell response to myelin oligodendrocyte glycoprotein (MOG), recently recognized as a potential target antigen in multiple sclerosis (MS), has not yet been characterized, in contrast to the T cell reactivity to other potential target antigens in MS such as myelin basic protein and proteolipid protein. Here, we show that the encephalitogenicity of the recombinant Ig-like domain of human MOG is associated, in H-2 b mice, with an immunodominant T cell reactivity against a single region of MOG spanning amino acids 35-55, accounting for the previously reported strong encephalitogenic activity of pMOG 35-55. A single injection of pMOG 35-55 with or without administration of pertussis toxin was sufficient to induce severe clinical experimental autoimmune encephalomyelitis (EAE) in H-2 b mice. Encephalitogenic pMOG 35-55-specific T cell lines derived from C3H.SW (V beta b) mice were diverse in their TCR V beta gene usage (V beta 1, V beta 6, V beta 8 and V beta 15), although V beta 8.2 was most predominantly expressed (48%). However, V beta 8 + T cells may only be part of the encephalitogenic MOG-specific T cell repertoire in H-2 b mice, as demonstrated by the susceptibility of C57L (V beta a) mice to disease induced by pMOG 35-55. Encephalitogenic T cell lines from V beta a mice were also diverse in their TCR V beta gene usage (V beta 1, V beta 2, V beta 6, V beta 14 and V beta 16). Such a heterogeneous TCT V beta gene expression by pMOG 35-55/I-A b-reactive T cells from both V beta a and V beta b H-2 b mice suggested multiple epitopes within pMOG 35-55. Analysis of the pattern of reactivity by pMOG 35-55-reactive T cells to a set of truncated peptides was not commensurate with independent nested epitopes, but revealed a requirement for recognition of a core sequence, YRSPFSRVV (pMOG 40-48). However, optimal stimulation was obtained with longer peptides, with each additional amino acid flanking either the N or the C terminus differentially increasing the stimulatory capacity of pMOG 40-48. Nonetheless, pMOG 40-48 was the minimal encephalitogenic epitope for both V beta a and V beta b mice. Thus, the T cell reactivity against the immunodominant encephalitogenic region of MOG is characterized by a diverse V beta gene usage and a requirement for the same core epitope. This pattern of reactivity may favor epitope-directed, rather than TCR-targeted, approaches to immunospecific therapy for MOG-related autoimmune disease.
 ...
PMID:Delineation of the minimal encephalitogenic epitope within the immunodominant region of myelin oligodendrocyte glycoprotein: diverse V beta gene usage by T cells recognizing the core epitope encephalitogenic for T cell receptor V beta b and T cell receptor V beta a H-2b mice. 889 62


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>