Evidences Indicate An Antigen-Specific Immune Reaction Is Responsible For The Formation And/Or The Maintenance Of MS Lesions
Chabas D, Liblau R
Pathol Biol (Paris) 2000 Feb;48(1):25-46
Groupe Hospitalier Pitie-Salpetriere, Paris, France
PMID# 10729910; UI# 20194103
This disease is characterized by the following:
- An infiltration of the White Matter of the Brain and Spinal Cord by inflammatory cells;
- The T and B-Lymphocytes, present in the lesions or in the CerebroSpinal Fluid of patients, show signs of activation; i.e., the classic IgG OligoClonal Bands of the CerebroSpinal Fluid (activation of B-Lymphocytes) and the presence of activation markers on the surface of the T-Lymphocytes;
- The presence of an association, and a linkage between the disease and the Genes of the HLA complex.
- The HLA molecules are implicated in the presentation of the Antigen to the T-Lymphocytes;
- Finally, it should be noted that the therapeutic approaches aimed at reducing (ImmunoSuppressants) or at modulating (Interferon-ß, Copolymer 1) the Immune Responses have a positive effect on this disease.
Whereas those treatments which activate the Immune System (Interferon-gamma) have a negative effect.
In Vivo Effects Of Recombinant-Interferon-ß-1b Treatment On PolyMorphonuclear Cell And Monocyte Functions And On T-Cell-Mediated AntiBacterial Activity In Relapsing/Remitting Multiple Sclerosis
Maffione AB, Tato E, Losito S, Nacci C, Mitolo V, Troiano M, Ruggieri M, Livrea P, Jirillo E
Immunopharmacol Immunotoxicol 2000 Feb;22(1):1-18
Univ of Bari, Medical School, Anatomy, Bari, Italy
PMID# 10737253; UI# 20199514
Treatment with Interferon (IFN-ß) has been proposed as a therapeutic approach in Multiple Sclerosis (MS) patients, mostly in view of its ImmunoModulating actions.
At the same time, evidence has been provided that MS patients exhibit PolyMorphoNuclear Cell (PMN) deficits, which can explain the increased susceptibility to infections in these subjects.
Here, in 28 patients with Relapsing/Remitting (RR) MS under treatment with recombinant (r)-IFN-ß PMN polarization and PMN and Monocyte (MO) Phagocytosis and killing, as well as T-Cell mediated AntiBacterial activity, were evaluated before treatment and over a period of nine months of treatment.
Our results point out an enhanced rate of polarization (both "spontaneous" or N-formyl-methionyl-leucyl-phenylalanine-induced) in MS patients. After r-IFN-ß-1b treatment the polarization rate was further increased.
On the contrary, PMN and MO phagocytosis and killing were depressed in comparison to controls and values were further reduced by r-IFN-ß-1b treatment.
In patients T-Cell mediated antibacterial activity was decreased at T0 and dramatically dropped in the course of r-IFN-ß-1b therapy.
N-Cadherin Influences Migration Of Oligodendrocytes On Astrocyte Monolayers
Schnadelbach O, Blaschuk OW, Symonds M, Gour BJ, Doherty P, Fawcett JW
Mol Cell NeuroSci 2000 Mar;15(3):288-302
Physiological Laboratory, Downing Street, Cambridge, CB2 3EG, United Kingdom
Oligodendrocyte cell migration is required for the development of the Nervous System and the repopulation of DeMyelinated lesions in the adult Central Nervous System.
We have investigated the role of the calcium-dependent Adhesion Molecules, the cadherins, in Oligodendrocyte-astrocyte interaction and Oligodendrocyte Progenitor migration.
Immunostaining demonstrated the expression of N-Cadherin on the surfaces of both Oligodendrocytes and Astrocytes, and Oligodendrocyte-like cells adhered to and spread on N-Cadherin substrates.
The blocking of Cadherin function by AntiSera or specific Peptides reduced adhesion of Oligodendroglia to Astrocyte Monolayers, diminished contact time between Oligodendrocyte processes and individual Astrocytes, and significantly increased the migration of Oligodendrocyte-like cells on Astrocyte Monolayers.
Furthermore, a soluble Cadherin molecule without adhesive properties increased Oligodendroglial proliferation on various ExtraCellular matrix substrates.
These data suggest that Cadherins are at least partially responsible for the poor migration-promoting properties of Astrocytes and that decreasing cell-cell adhesion might effect repopulation of DeMyelinated Multiple Sclerosis lesions by Oligodendrocyte progenitors.
Copyright 2000 Academic Press.
Elevated CD40 Ligand Expressing Blood T-Cell Levels In Multiple Sclerosis Are Reversed By Interferon-beta Treatment
Teleshova N, Bao W, Kivisakk P, Ozenci V, Mustafa M, Link H
Scand J Immunol 2000 Mar;51(3):312-20
Karolinska Institutet, Huddinge Univ Hospital, Division of Neurology, NeuroImmunology Unit, Stockholm, Sweden
PMID# 10736102; UI# 20200799
Myelin protein reactive CD4+ T-Cells are considered to be involved in the proposed ImmunoPathoGenesis of Multiple Sclerosis (MS). One particularly important molecule for T-Cell activation is the CD40L (gp39) that is expressed on the surface of T-Cells.
This study focuses on the CD40 and the CD40L expression on MonoNuclear Cells prepared from blood from patients with MS, Other Neurological Diseases (OND) and healthy subjects.
Immunostaining followed by a three channel flow cytometry was adopted. Patients with MS had higher levels of CD3+CD40L+, CD4+CD40L+ and CD8+CD40L+ T-Cells compared to patients with OND and healthy subjects.
Cross-sectional comparisons revealed that the elevation of CD40L+ T-Cell subtypes was confined to the patients with untreated MS and not observed in the patients with MS treated with Interferon-beta (IFN-ß).
Follow up studies showed that levels of CD3+CD40L+ and CD4+CD40L+ T-Cells decreased in individual patients after the initiation of the IFN-ß treatment.
The enhanced expression of CD40L on CD3+, CD4+ and CD8+ T-Cells in patients with MS may implicate a role for this molecule in disease ImmunoPathoGenesis.
Neuregulin: An Oligodendrocyte Growth Factor Absent In Active Multiple Sclerosis Lesions
Viehover A, Miller RH, Park SK, Fischbach G, Vartanian T
Dev NeuroSci 2001;23(4-5):377-86
Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Neurology, Boston, MA, USA
Multiple Sclerosis (MS) is an Inflammatory Demyelinating Disease of the Central Nervous System (CNS) which results in DeMyelination and Axonal injury.
Conventional therapy for MS is Immune suppression in the absence of agents that promote Neural and Glial survival or ReMyelination.
Neuregulins are a family of Ligands that exert Trophic effects on both Neurons and Glia.
Using mice bearing a null mutation in the Neuregulin Gene, here we demonstrate that Neuregulins are necessary for the normal development of Oligodendrocytes.
In addition, Neuregulins are produced in the normal human CNS by Astrocytes as well as Neurons. Astrocyte-derived Neuregulin is functionally active in bioassays and exists in secreted and membrane-associated beta-Isoforms.
In active and chronic active MS lesions, however, the expression of Astrocyte Neuregulin is dramatically reduced. The absence of Neuregulin in active MS lesions may contribute to the paucity of ReMyelination in MS.
Copyright 2001 S. Karger AG, Basel