Selection for T-cell receptor V beta-D beta-J beta gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis.
Conversion to MS was positively associated with the DRB1*1501.DQA1*0102.DQB1*0602 haplotype, but the influence of HLA was only significant in patients with disseminated brain lesions at presentation (MRI positive); MS developed in 86% of MRI-positive, DRB1*1501-positive patients compared with 55% of MRI-positive, DRB1*1501-negative patients (p < 0.025).
Conversion to MS was positively associated with the DRB1*1501.DQA1*0102.DQB1*0602 haplotype, but the influence of HLA was only significant in patients with disseminated brain lesions at presentation (MRI positive); MS developed in 86% of MRI-positive, DRB1*1501-positive patients compared with 55% of MRI-positive, DRB1*1501-negative patients (p < 0.025).
To evaluate the role of candidate genes in the susceptibility to multiple sclerosis (MS) and describe the role of T-cell receptor (TCR) gene rearrangements in the MS brain lesion in identifying a major target of the immune response in this disease.
Conversion to MS was positively associated with the DRB1*1501.DQA1*0102.DQB1*0602 haplotype, but the influence of HLA was only significant in patients with disseminated brain lesions at presentation (MRI positive); MS developed in 86% of MRI-positive, DRB1*1501-positive patients compared with 55% of MRI-positive, DRB1*1501-negative patients (p < 0.025).
The TCR V gene usage and CDR3s of these MBP-reactive hprt-T cell clones are homologous to TCRs from other T cells relevant to MS, including T cells causing experimental allergic encephalomyelitis (EAE) and T cells found in brain lesions and in the cerebrospinal fluid (CSF) of MS patients.
The TCR V gene usage and CDR3s of these MBP-reactive hprt-T cell clones are homologous to TCRs from other T cells relevant to MS, including T cells causing experimental allergic encephalomyelitis (EAE) and T cells found in brain lesions and in the cerebrospinal fluid (CSF) of MS patients.
The TCR V gene usage and CDR3s of these MBP-reactive hprt- T-cell clones are homologous to TCRs from other T-cells relevant to MS, including T-cells causing experimental allergic encephalomyelitis (EAE) and T-cells found in brain lesions and in the cerebrospinal fluid (CSF) of MS patients.
The TCR V gene usage and CDR3s of these MBP-reactive hprt- T-cell clones are homologous to TCRs from other T-cells relevant to MS, including T-cells causing experimental allergic encephalomyelitis (EAE) and T-cells found in brain lesions and in the cerebrospinal fluid (CSF) of MS patients.
In four of four MS and two of three TB patients, the oligoclonal sequences in the HSP70+ T cell lines were identical to one another and to a dominant sequence previously detected in MS brain lesions.
The TCR V gene usage and CDR3s of these MBP-reactive hprt- T-cell clones are homologous to TCRs from other T-cells relevant to MS, including T-cells causing experimental allergic encephalomyelitis (EAE) and T-cells found in brain lesions and in the cerebrospinal fluid (CSF) of MS patients.
Lymphotoxin-alpha (LT-alpha) and tumour necrosis factor-alpha (TNF-alpha) promote inflammation in autoimmune diseases and have been detected in the multiple sclerosis (MS) brain lesions and blood, suggesting these cytokines are also present in the cerebrospinal fluid (CSF).
Lymphotoxin-alpha (LT-alpha) and tumour necrosis factor-alpha (TNF-alpha) promote inflammation in autoimmune diseases and have been detected in the multiple sclerosis (MS) brain lesions and blood, suggesting these cytokines are also present in the cerebrospinal fluid (CSF).
To better understand the nature of the T cell response in this disease, we analyzed TCR expression in the brain lesions using PCR for quantitative assessment of TCRBV gene transcripts, together with size and sequence analysis of the third complementarity-determining region (CDR3) of the dominant TCR rearrangements.
Inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-4, interleukin-6 and interferon-gamma) gene expression was increased in multiple sclerosis brain lesions, as has been reported previously, but much less so in CER brain lesions.
To better understand the nature of the T cell response in this disease, we analyzed TCR expression in the brain lesions using PCR for quantitative assessment of TCRBV gene transcripts, together with size and sequence analysis of the third complementarity-determining region (CDR3) of the dominant TCR rearrangements.
A major proportion of the IFNgamma mRNA expressing lymphocytes belonged to the CD4+ lineage, which concords with the cellular composition of MS brain lesions, findings in experimental models and the HLA class II haplotype association in MS.
Surprisingly, we found that lack of p53 expression induces apoptotic brain lesions, accompanied by learning deficiency and behavioral alterations. p53-deficient mice show an unexpected overexpression of p21(waf1) with subsequent down-regulation of PS1 in their brains.