Lymphocyte subsets in multiple sclerosis A study with two-colour fluorescence analysis

Bongioanni, Paolo; Fioretti, Cristina; Vanacore, Renato; Bianchi, Fabrizio; Lombardo, Francesco; Ambrogi, F; Meucci, Giuseppe

doi:10.1016/0022-510x(96)00030-5

Cited by 22 publications

(8 citation statements)

References 35 publications

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“…well as nonclassical MHC molecules such as CD1, in conjunction with enhanced antigen presentation due to specific antibody (54), represents a mechanism whereby CNP-derived (lipo-) peptides may be presented for immune surveillance not only to CD4ϩ or CD8ϩ T cells but possibly also to T␥/␦ cells which are prominent in MS lesions (55) and preferentially recognize nonpeptide antigens (56) including the types of moieties by which CNP is modified posttranslationally. The expression of CNP by lymphocytes may likewise have relevance to the cellular immune derangements described in peripheral blood of MS patients (20,21).…”

Section: Discussionmentioning

confidence: 99%

“…Finally and unexpectedly, the response to CNP is chiefly IgM, is temporally persistent, and is present in serum as well as CSF. This indicates that as for the cellular immune response (20,21), pronounced humoral immune activation in MS also occurs systemically even if the major clinical and pathological consequences are manifest exclusively in the CNS.…”

Section: Introductionmentioning

confidence: 99%

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Dual implication of 2',3'-cyclic nucleotide 3' phosphodiesterase as major autoantigen and C3 complement-binding protein in the pathogenesis of multiple sclerosis.

Walsh¹,

Murray²

1998

J. Clin. Invest.

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Multiple sclerosis (MS) is characterized by intra-blood-brain barrier immunoglobulin synthesis that persists lifelong. Subcellular fractionation and two-dimensional electrophoresis were used in conjunction with immune precipitation and immunoblotting to identify antigenic determinants for this immunoglobulin. We report that 2 Ј ,3 Ј-cyclic nucleotide 3 Јphosphodiesterase (CNP), a protein associated with oligodendrocyte/myelin membranes, also present in lymphocytes and retina, is one major target for the humoral response. Antibodies to CNP are detected in sera of 74% of MS patients. The antibodies are IgM and are present in serum in high titer as well as in cerebrospinal fluid. The antibody response is temporally persistent, consistent with systemic immune activation and persistent antigenic stimulation. Moreover, CNP is isolated as an immune complex from MS brain. CNP is expressed as two isoforms, with CNPII identical to CNPI but with a 20-amino acid extension at the amino terminus of CNPII; however, the antibody response is exclusively restricted to CNPI. In contrast, both isoforms bind the C3 complement, providing a plausible mechanism in MS central nervous system (CNS) for opsonization of myelin membrane CNP, mediated via the C3 receptor, and phagocytosis of CNP-Ig immune complexes, mediated by membrane Ig Fc receptors of macrophages and CNS microglia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dual implication of 2',3'-cyclic nucleotide 3' phosphodiesterase as major autoantigen and C3 complement-binding protein in the pathogenesis of multiple sclerosis.

Walsh¹,

Murray²

1998

J. Clin. Invest.

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“…The peripheral blood (1 ml/mouse) was collected in heparinized tubes for all of the experiments [45]. One hundred microliters of blood was incubated in the dark for 30 min with the following antigens: 5 μl CD3e-PerCP, 2 μl CD4-FITC and 5 μl CD8a-PE.…”

Section: Methodsmentioning

confidence: 99%

Nanotoxicity comparison of four amphiphilic polymeric micelles with similar hydrophilic or hydrophobic structure

Zhao

Wang

et al. 2013

Part Fibre Toxicol

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BackgroundNanocarriers represent an attractive means of drug delivery, but their biosafety must be established before their use in clinical research.ObjectivesFour kinds of amphiphilic polymeric (PEG-PG-PCL, PEEP-PCL, PEG-PCL and PEG-DSPE) micelles with similar hydrophilic or hydrophobic structure were prepared and their in vitro and in vivo safety were evaluated and compared.MethodsIn vitro nanotoxicity evaluations included assessments of cell morphology, cell volume, inflammatory effects, cytotoxicity, apoptosis and membrane fluidity. An umbilical vein cell line (Eahy.926) and a kind of macrophages (J774.A1) were used as cell models considering that intravenous route is dominant for micelle delivery systems. In vivo analyses included complete blood count, lymphocyte subset analysis, detection of plasma inflammatory factors and histological observations of major organs after intravenous administration to KM mice.ResultsAll the micelles enhanced inflammatory molecules in J774.A1 cells, likely resulting from the increased ROS levels. PEG-PG-PCL and PEEP-PCL micelles were found to increase the J774.A1 cell volume. This likely correlated with the size of PEG-PG-PCL micelles and the polyphosphoester structure in PEEP-PCL. PEG-DSPE micelles inhibited the growth of Eahy.926 cells via inducing apoptosis. This might relate to the structure of DSPE, which is a type of phospholipid and has good affinity with cell membrane. No evidence was found for cell membrane changes after treatment with these micelles for 24 h. In the in vivo study, during 8 days of 4 time injection, each of the four nanocarriers altered the hematic phase differently without changes in inflammatory factors or pathological changes in target organs.ConclusionsThese results demonstrate that the micelles investigated exhibit diverse nanotoxicity correlated with their structures, their biosafety is different in different cell model, and there is no in vitro and in vivo correlation found. We believe that this study will certainly provide more scientific understandings on the nanotoxicity of amphiphilic polymeric micelles.

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“…The frequency of B-1 cells has been demonstrated to correlate with disease activity, circulating levels of autoantibodies against myelin basic protein and the number of gadolinium-enhancing magnetic resonance imaging (MRI) lesions in patients with relapsing-remitting (RR) MS [26]. Patients with progressive MS were found to have a significantly higher percentage of B-1 cells than patients with RR disease [27]. A recent study reported an increase in CD5 − B cells (B-2 or B-1b) in patients with MS, but similar numbers of CD5 + B-1a cells among patients with clinically definite MS, patients with a clinically isolated syndrome (CIS) suggestive of MS and control patients with noninflammatory neurological diseases [28].…”

Section: Introductionmentioning

confidence: 99%

Role of CD5⁺B-1 cells in EAE pathogenesis

2008

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Hybridoma cell lines producing natural autoantibodies (NAA), generated from A.SW mice with progressive experimental autoimmune encephalomyelitis (P-EAE), have been shown to cause demyelination and renal pathology when injected into naïve mice. To investigate the relative contribution of these antibodies to disease pathogenesis, B-1 cells, the major producers of NAA, were depleted by hypotonic shock. Depletion of B-1 cells during the effector phase of EAE significantly decreased the severity of demyelination and overall pathology in the brain. There was also a decreased incidence of P-EAE and a decrease in clinical score. Depletion during the induction phase of the disease resulted in an increase in the incidence of P-EAE and in the clinical score. Overall, B-1 cells were found to modulate EAE pathogenesis.

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Lymphocyte subsets in multiple sclerosis A study with two-colour fluorescence analysis

Cited by 22 publications

References 35 publications

Dual implication of 2',3'-cyclic nucleotide 3' phosphodiesterase as major autoantigen and C3 complement-binding protein in the pathogenesis of multiple sclerosis.

Dual implication of 2',3'-cyclic nucleotide 3' phosphodiesterase as major autoantigen and C3 complement-binding protein in the pathogenesis of multiple sclerosis.

Nanotoxicity comparison of four amphiphilic polymeric micelles with similar hydrophilic or hydrophobic structure

Role of CD5⁺B-1 cells in EAE pathogenesis

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Lymphocyte subsets in multiple sclerosis A study with two-colour fluorescence analysis

Cited by 22 publications

References 35 publications

Dual implication of 2',3'-cyclic nucleotide 3' phosphodiesterase as major autoantigen and C3 complement-binding protein in the pathogenesis of multiple sclerosis.

Dual implication of 2',3'-cyclic nucleotide 3' phosphodiesterase as major autoantigen and C3 complement-binding protein in the pathogenesis of multiple sclerosis.

Nanotoxicity comparison of four amphiphilic polymeric micelles with similar hydrophilic or hydrophobic structure

Role of CD5+B-1 cells in EAE pathogenesis

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Role of CD5⁺B-1 cells in EAE pathogenesis