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C Vandevyver

Publications and source records attributed to C Vandevyver.

36 records · Page 2Linked to original sources
PubMed1995

Increased frequency of gamma delta T cells in cerebrospinal fluid and peripheral blood of patients with multiple sclerosis. Reactivity, cytotoxicity, and T cell receptor V gene rearrangements.

Infiltrating gamma delta T cells are potentially involved in the central nervous system demyelination in multiple sclerosis (MS). To further study this hypothesis, we analyzed the frequency and functional properties of gamma delta T cells in peripheral blood (PB) and paired cerebrospinal fluid (CSF) of patients with MS and control subjects, including patients with other neurologic diseases (OND) and healthy individuals. The frequency analysis was performed under limiting dilution condition using rIL-2 and PHA. After PHA stimulation, a significantly increased frequency of gamma delta T cells was observed in PB (14.7 x 10(-4)) and in CSF (15.8 x 10(-4)) of MS patients as compared with 4.3 x 10(-4) in PB and 3.9 x 10(-4) detected in CSF of patients with OND. The frequency was represented equally in OND patients and normal individuals. Similarly, the IL-2-responsive gamma delta T cells occurred at a higher frequency in PB of control subjects (1.1 x 10(-4)) in OND patients and 1.5 x 10(-4) in normal individuals). Forty-three percent (13 of 30) of the gamma delta T cell clones isolated from PB and CSF of MS patients responded to heat shock protein (HSP70) but not HSP65, whereas only 2 of 30 control gamma delta T cell clones reacted to the HSP. The majority of the gamma delta T cell clones were able to induce non-MHC-restricted cytolysis of Daudi cells. All clones displayed a substantial reactivity to bacterial superantigens staphylococcal enterotoxin B and toxic shock syndrome toxin-1, irrespective of their gamma delta V gene usage. Furthermore, the gamma delta T cell clones expressed predominantly TCRDV2 and GV2 genes (26 of 35 clones), whereas the clones derived from CSF of MS patients expressed either DV1 or DV2 genes. The obtained gamma delta clones, in general, represented rather heterogeneous clonal origins, even though a predominant clonal origin was found in a set of 10 gamma delta clones derived from one patient with MS. The present study provides new evidence supporting a possible role of gamma delta T cells in the secondary inflammatory processes in MS.

Base Sequence↗
PubMed1995

Clonal expansion of myelin basic protein-reactive T cells in patients with multiple sclerosis: restricted T cell receptor V gene rearrangements and CDR3 sequence.

Myelin basic protein (MBP)-reactive T cells are thought to play an important role in the pathogenesis of multiple sclerosis (MS). In some patients with MS, these autoreactive T cells display a limited heterogeneity in their epitope recognition and T cell receptor (TCR) variable (V) gene usage. These individual-dependent properties of MBP-reactive T cells have led to the speculation that they may represent clonal expansion in vivo in some MS patients. In the present study, 51 MBP-reactive T cell clones derived from patients with MS and healthy individuals were examined for their epitope recognition and the TCR V alpha and V beta gene rearrangements. The V gene junctional region sequences of identified alpha and beta genes were further analyzed to probe their clonal origins, as the sequences are unique for individual clones. Our data showed that 26 clones derived from nine patients with MS shared a predominant reactivity to the immunodominant regions of MBP, 84-102, 110-129 and 143-168, and used various TCR V alpha and V beta rearrangements. The V gene usage of the clones was restricted to certain V alpha V beta combination(s) in a given MS patient, but varied among different patients. The sequence analysis revealed that the clones generated from a given patient shared a limited or a single junctional region sequence pattern(s), indicating their oligoclonal or monoclonal origin(s). In contrast, 25 MBP-reactive T cell clones derived from normal individuals exhibited unfocused epitope recognition and V gene usage. Thus, the limited heterogeneity of MBP-reactive T cells in their structural and functional characteristics reflects their clonal expansion in vivo in some patients with MS.

Amino Acid Sequence↗
PubMed1995

Superantigen reactivity of gamma delta T cell clones isolated from patients with multiple sclerosis and controls.

gamma delta T cells have been implicated as playing a role in the demyelinating processes of multiple sclerosis (MS). However, the nature of the ligands which lead to activation and accumulation of gamma delta T cells in the brain lesions remains unknown. This study was undertaken to examine whether gamma delta T cells derived from cerebrospinal fluid and blood of MS patients could be stimulated by bacterial superantigens: staphylococcal enterotoxins A and B and toxic shock syndrome toxin-1. A panel of 16 gamma delta T cell clones isolated from MS patients and controls was found to react with the superantigens used at a nanogram range and displayed specific cytotoxic activity toward target cells pulsed with the corresponding superantigens. The responses of the gamma delta T cell clones did not require MHC-matched accessory cells and were not blocked by antibodies to the MHC molecules, suggesting a non-MHC restricted interaction. The superantigen reactivity was associated with both V delta 2+/V gamma 2+ and V delta 1+/V gamma 1+ subsets, reportedly found in the MS lesions. Our data suggest an alternative pathway which may account for gamma delta T cell activation in MS.

B-Lymphocytes↗
PubMed1995

Importance of HLA-DRB1 and DQA1 genes and of the amino acid polymorphisms in the functional domain of DR beta 1 chain in multiple sclerosis.

The association of some HLA class II alleles with multiple sclerosis (MS) has been amply documented. In the present study the role of HLA class II haplotypes and genotypes and of polymorphic amino acids at the DR beta 1 locus, located in the antigen binding groove and the CD4 binding domain of the DR beta 1 chain, were studied in 78 unrelated Caucasian chronic progressive MS (CP MS) patients and 204 controls. The results confirmed the positive association of the DRB1*1501 allele and through linkage also of the DRB1*1501-DQA1*0102 haplotype with MS. In addition, the results showed that the DRB1*1501/DRB1*0400 or DR beta 1Ala71+ His13+ genotype conferred the highest relative risk for MS (RR = 9.14). Alleles encoding for DR beta 1Phe47+, DR beta 1Asp70+ and DR beta 1Thr140+, DQ alpha 1Phe25+, DQ alpha 1Leu69+ residues were protective and the highest protection (RR = 0.24) was provided by the DR beta 1(Phe47+)-DQ alpha 1Phe25+ and DR beta 1(Ser13+)-DQ alpha 1Phe25+ haplotypes. Our results suggest that both DQ and DR alpha beta heterodimers might contribute to the increased or decreased risk to develop MS by the shape of their antigen-binding groove.

Adult↗
PubMed1995

Activation and clonal expansion of human myelin basic protein-reactive T cells by bacterial superantigens.

Autoreactive T cells specific for myelin basic protein (MBP) are part of the normal T cell repertoire and are present both in patients with multiple sclerosis (MS) and healthy individuals. There is evidence suggesting in vivo activation and persistent clonal expansion of MBP-reactive T cells in MS. This study was undertaken to investigate the potential role of bacterial superantigens (SA) in the activation of MBP-reactive T cells. Twenty-seven MBP-reactive T cell clones generated from 10 MS patients and one normal individual were examined for reactivity to SA, in association with their T cell receptor V beta gene usage. The majority of the clones responded to at least one of the SA tested, staphylococcal enterotoxins (SEA and SEB) and toxic shock syndrome toxin-1 (TSST-1). The clones reactive to SEA and SEB expressed various V beta genes while T cell reactivity to TSST-1 correlated with the V beta 2 expression. Furthermore, circulating MBP-reactive T cells could be expanded from lymphocyte cultures primarily exposed to respective SA in more than 50% of MS patients and normal individuals tested. However, activation and expansion of circulating MBP-reactive T cells by SA was not directly associated with the disease. This study lends support to the potential role of SA in the activation of MBP-reactive T cells and suggests that an altered regulatory mechanism may account for further expansion and persistence of MBP-reactive T cells in MS.

Adult↗
PubMed1995

Peptide transporter genes (TAP) polymorphisms and genetic susceptibility to rheumatoid arthritis.

The association of rheumatoid arthritis (RA) with HLA-DRB1 alleles indicates that at least one RA susceptibility gene is linked to the HLA class II region. Transporter associated with protein processing (TAP) genes, which lie upstream of the HLA-structural genes, may also contribute to disease susceptibility. We investigated polymorphisms of the peptide transporter genes, TAP 1 and TAP 2, by PCR-ASO hybridization techniques in 82 RA patients and 66 control individuals. Although there was a suggestion of linkage between some TAP polymorphisms and RA, these seem to be dependent on HLA-DRB1*04, since these positive associations disappeared when HLA-DRB1*04 positive RA patients and controls were compared. Furthermore, no particular TAP allele or haplotype was associated with any clinical or immunological subgroup of RA. We conclude that the TAP genes do not have a major influence on susceptibility to RA in the European Caucasian population.

Adult↗
PubMed1995

Quantification of cytokine mRNA expression by RT-PCR and electrochemiluminescence.

Variable gene expression constitutes a major mechanism for controlling cell development and cell function. To investigate these changed mRNA levels, a sensitive and quantitative assay is required. We describe a quick and easy method to quantify specific mRNAs by a combination of PCR and an electrochemiluminescent (ECL) detection of the amplified products. Total cellular RNA is reverse-transcribed and amplified with a biotinylated forward primer and a Tris (2,2'-bipyridine) ruthenium (II) (TBR)-labeled reverse primer. The amplification product is captured on streptavidin-coated paramagnetic beads and quantified by ECL detection using the QPCR system 5000. The results can be converted to quantitative values with an external standard curve. This method permits accurate and reliable quantitation of cytokine mRNA expression.

Clone Cells↗
PubMed1995

Quantitative analysis of lymphokine mRNA expression by an automated, non-radioactive method.

Variable gene expression, thus giving rise to variable mRNA levels, constitutes a major mechanism for controlling cell development and cell function. In order to investigate these changed mRNA levels, a sensitive and quantitative assay is required. A quick and easy method is described to quantify specific mRNA's by a combination of the polymerase chain reaction (PCR) and an electro-chemiluminescenct (ECL) detection of the amplified products. Total cellular RNA is reverse transcribed and amplified with a biotinylated forward primer and a TBR (Tris (2,2'-bipyridine) ruthenium (II)) labelled reverse primer. The amplification product is captured on streptavidin-coated paramagnetic beads and quantified by ECL detection using the QPCR system 5000. The results can be converted to quantitative values with an external standard curve. In the present study, cytokine mRNA expression in T lymphocytes was quantified. Cytokine mRNA was measured at the attomolar range in a dynamic range up to three orders of magnitude. The ECL detection is quantitative, rapid and accurate.

Base Sequence↗
PubMed1994

HLA and T-cell receptor polymorphisms in Belgian multiple sclerosis patients: no evidence for disease association with the T-cell receptor.

There are compelling data to indicate that the susceptibility to multiple sclerosis (MS) is inherited, at least in part. Particular HLA genotypes may be associated with MS and recently also polymorphisms in the T-cell receptor (TCR) genes have been reported to correlate with the disease; however, these data have been difficult to confirm. We investigated the TCRA and TCRB chain genes of HLA-typed Belgian CP MS patients employing four DNA restriction fragment length polymorphisms (RFLPs) detected with TCR constant (TCRAC1, TCRBC2) and variable (TCRBV8, TCRBV11) gene segments. Similar frequencies in patients and controls were observed for all RFLPs studied. Although the HLA DR2 genotype was significantly associated with MS, no interactive effects were seen with MS, DR2, TCRAC1, TCRBC2 and TCRBV alleles. We conclude that, while a clear association with HLA DR2 is observed, little convincing evidence exists for an association of CP MS with RFLPs of the TCRA or TCRB chain genes.

Alleles↗
PubMed1994

Myelin basic protein gene polymorphism is not associated with chronic progressive multiple sclerosis.

In the present study a tetranucleotide (TGGA)n repeat polymorphism 5' to the myelin basic protein (MBP) gene was evaluated in a group of HLA-class II-typed, chronic progressive multiple sclerosis (MS) patients. This polymorphism has been reported by others to be associated with MS. Contrary to these reports we observed similar allele frequencies in patients and controls. Our results indicate that there is no association between MS and a polymorphism 5' to the MBP gene.

Alleles↗
PubMed1994

TAP 1 and TAP 2 transporter gene polymorphisms in multiple sclerosis: no evidence for disease association with TAP.

Multiple sclerosis (MS) is known to be associated with HLA-DR2, but it is possible that additional major histocompatibility complex (MHC) genes confer disease susceptibility. The most recent candidate genes for MHC-encoded susceptibility are the TAP genes, which are located between the HLA-DQ and DP loci, and encode for proteins believed to transport antigenic peptides from the cytoplasm into the endoplasmic reticulum. We studied TAP 1 and TAP 2 gene polymorphisms in 65 chronic progressive MS patients and 66 healthy subjects. No significant differences in the frequencies of TAP polymorphisms were observed between both groups. These data suggest that TAP is not a susceptibility gene for MS and that the disease-predisposing haplotype does not extend as far as TAP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Polymorphism of the tumour necrosis factor beta gene in multiple sclerosis and rheumatoid arthritis.

We evaluated the TNF-beta gene polymorphism in two HLA-associated autoimmune diseases, multiple sclerosis (MS) and rheumatoid arthritis (RA). The TNF-beta allele and genotype frequencies were not significantly different in the patient populations, compared to controls. An increased frequency of the TNF-beta*2 allele was observed in HLA-DR2+ vs. HLA-DR2- MS patients. No such association was seen in HLA-DR4+ RA patients.

Alleles↗
PubMed1994

T cell receptor delta locus polymorphism in rheumatoid arthritis.

In order to identify new susceptibility markers for Rheumatoid Arthritis (RA), we analysed the dinucleotide repeat polymorphism at the T cell receptor delta locus (TCRD) in 65 RA patients and 99 healthy Belgian controls. A significant under-representation of the A4-A5 TCRD genotype was observed in the RA population.

Alleles↗
PubMed1994

HLA class II and T-cell receptor beta chain polymorphisms in Belgian patients with rheumatoid arthritis: no evidence for disease association with the TCRBC2, TCRBV8 and TCRBV11 polymorphisms.

OBJECTIVES: To investigate whether T-cell receptor (TCR) beta chain germline alleles, either alone or in combination with a particular HLA-genotype, are associated with rheumatoid arthritis (RA). METHODS: Three restriction fragment length polymorphisms (RFLPs), detected with TCR constant (TCRBC2) and variable (TCRBV8, TCRBV11) gene segments were analysed in a representative group of Belgian, HLA class II-typed patients with RA, and in a group of Belgian control subjects. RESULTS: The study confirmed the known association of RA with the HLA-DRB1*0401/0404 genotype (RR = 2.14, 95% CI = 1.16-4.00) in the Belgian RA population. This association was even more pronounced in the patients with more severe RA (RR = 3.26, 95% CI = 1.55-6.89). These data suggest that the HLA-DRB1*04 genotype can be used as a marker for disease severity. Similar frequencies in patients and controls were observed for all TCRB RFLPs studied, and this was in spite of subgrouping the RA population according to criteria for disease stratification. CONCLUSION: While a clear association with HLA DRB1*0401/0404 is observed, no interactive effects were seen with RA, DR4, TCRBC2 and TCRBV alleles, implying that the combined presence of these polymorphic markers does not cause an increased susceptibility to RA, and does not predispose for more aggressive RA, nor for familial aggregation of the disease. These results argue against the hypothesis that TCRB polymorphisms play a crucial role in the susceptibility for RA.

Adult↗
PubMed1993

Development and functional characterization of a murine/human chimeric antibody with specificity for the human interleukin-2 receptor.

A murine/human chimeric antibody, with specificity for the human interleukin-2 receptor, was developed by genetic engineering. For this purpose, the light and heavy chain variable region exons encoding the murine monoclonal antibody 2C8 were isolated and inserted into expression vectors containing the human kappa and gamma-1 constant regions. After transfection by electroporation of the chimeric genes into murine Sp 2/0 hybridoma cells, transfectomas secreting the complete chimeric antibody were selected. The chimeric antibody has similar binding properties as the original murine antibody. The in vitro cytotoxic effects of the murine and the chimeric antibodies were compared.

Amino Acid Sequence↗