Experimental Allergic EncephaloMyelitis (EAE) is a frequently employed animal model of the human disease Multiple Sclerosis. EAE can be induced by adoptive transfer of CD4⁺ T-Cells that are specific for Central Nervous System (CNS) Antigens, typically Myelin proteins.

Although the Pathogenic mechanism or mechanisms responsible for the clinical signs and histological changes in EAE and Multiple Sclerosis are not fully defined, the entry of T-Lymphocytes and Antigen recognition within the CNS are required.

The present study describes the participation of a novel cell surface molecule with properties suggesting a role in cell-cell adhesion or co-stimulation, or both, in the development of EAE in the rat.

The molecule is defined by the unique MonoClonal AntiBody (mAb) TLD-4A2. The TLD-4A2 Antigen is present on resting and activated T-Lymphocytes, activated CNS Endothelial Cells, and Microglia.

The Antigen is normally distributed in many tissues including Lymph Node, Thymus, and Spleen, as well as in the inflamed CNS. Both its pattern of tissue distribution and ImmunoPrecipitation and ImmunoBlotting studies suggest that the TLD-4A2 Antigen is a novel molecule.

Treatment of rats with the purified 4A2 mAb resulted in the inhibition of the clinical signs of EAE and also decreased the number T-Cells and Macrophages accumulating in the CNS Parenchyma.

TLD-4A2 AntiBody did not seem to directly interfere with T-Cell viability in vivo, as demonstrated by the ability to recover and stimulate CD4⁺ Encephalitogenic T-Cells from Cervical Lymph Nodes of 4A2-treated animals. In vitro, the AntiBody partially blocked T-Cell proliferation assays.

These data suggest that the TLD-4A2 mAb recognizes a novel molecule expressed on Lymphocytes, Endothelial Cells, and MMacrophages that may play a role in hematogenous cell traffic and the initiation of CNS inflammation.

MyeloPerOxidase (MPO) generates Hypochlorous Acid and other reactive Oxygen intermediates leading to tissue damage.

MPO is expressed in Macrophages-Microglia in Multiple Sclerosis (MS) lesions. A G-->A substitution that abolishes an SP1 transcription factor consensus sequence in the promoter reduces Gene expression.

We studied the association of the Genetic variant with MS. We did not find an association with gender, age at onset, susceptibility to, or the course and severity of MS in a population-based sample of 122 patients from Olmsted County.

Co-stimulation of T-Cells by B7-1, a protein that is expressed on Antigen-Presenting Cells, favors a T-Helper Type1 (Th1) Cellular Response. Th1/Th2 bias may influence disease susceptibility or course of MS.

We screened the entire coding sequence as well as the 5'- and 3'-untranslated regions of the B7-1 Gene using a mutation scanning technique, DideoxyFingerprinting, in DNA from 111 patients with MS from Olmsted County, Minnesota. We identified five Genetic variants.

None alter protein structure nor have apparent functional significance. Selected variants of sufficient frequency were tested for an association with course and severity of MS and one was tested for an association with susceptibility; none of the association tests were positive.

The expression of Fas-Ligand (Fas-L) on Microglia could be relevant in Multiple Sclerosis ImmunoPathology.

The present study was performed to evaluate in vitro the expression of Fas-L in human Microglial Cells both unstimulated and after stimulation with IFN-γ, ß-IFN-1b and ß-IFN-1b+IFN-γ.

Cells were stimulated for 6,12, 24 and 48 h. Surface Fas-L was evaluated by flow cytometry, total Fas-L by Western blot, whereas mRNA for Fas-L was measured by RT-PCR. We also evaluated the capacity of Microglial Cells to induce, in vitro, Apoptosis on Fas-positive T-Leukemia Jurkat Cells.

Our results showed a constitutive expression of Fas-L on Microglia. IFN-γ downregulated the expression of the molecule, while ß-IFN-1b and ß-IFN-1b+IFN-γ did not.

The amount of surface Fas-L was related to the ability of Microglial Cells to induce Apoptosis in Fas-positive targeT-Cells, which was partly inhibited by blockade of the Fas-Fas-L pathway.

T-Cell responses to Myelin Basic Protein (MBP) are potentially involved in the PathoGenesis of Multiple Sclerosis (MS).

In this study, we demonstrated that subcutaneous inoculations with irradiated autologous MBP-reactive T-Cell clones (T-Cell Vaccination) elicited CD8⁺ anti-idiotypic T-Cell responses and CD4⁺ Th2 Cell responses in patients with MS.

Both regulatory cell types induced by T-Cell Vaccination contributed to the inhibition of MBP-reactive T-Cells while they differed in the recognition pattern and functional properties.

We describe for the first time that the Th2 regulatory cells reacted with activated but not resting T-Cells in the context of MHC Class II molecules and inhibited the proliferation of MBP-reactive T-Cells through the secretion of IL-4 and IL-10.

The T-T-Cell interaction mediated by Th2 regulatory cells was independent of the Antigen specificity of activated T-Cells.

The findings have important implications for our understanding of the regulatory mechanism induced by T-Cell Vaccination.

We conducted a prospective study among 166 Multiple Sclerosis (MS) patients (103 from an university hospital, 63 from a MS rehabilitation center) to assess the properties of the French version of the Multiple Sclerosis Quality Of Life - 54 items (MS QOL-54) which combines the MOS SF36 together with MS specific items.

The SF-36 had been translated into French through the IQOLA project. We translated and adapted the MS specific items with the help of three different teams.

The translation into French has an addition of five items, because we kept the MS specific items of an earlier unpublished form. Acceptability is excellent with a response rate over 90p.100.

Test-retest reliability is good except for the "role limitation-emotional" scale of the SF-36. Construct validity, based on factor analysis, shows no change in the SF-36 internal consistency and the specific items provided their own information.

External validity, tested against both medical (Expanded Disability Status Scale, Kurtzke scale, Mini-Mental-State and disease stage) and rehabilitation (Functional Independence Measure) parameters is excellent.

The French MS QOL questionnaire contains 59 items including both the SF-36 and the MS QOL-54 items. This will permit international comparisons of MS patients' care and therapy.

IL-10 and TGF-ß1 are important ImmunoRegulatory Cytokines associated with clinical remissions in Multiple Sclerosis and amelioration of Experimental Allergic EncephaloMyelitis (EAE).

IL-10 and TGF-ß1 have previously been shown to prevent the development of EAE. Here, we study effects of IL-10 and TGF-ß1 in ongoing EAE.

When IL-10 or TGF-ß1 was administered by the nasal route from day 0 to day 7 postimmunization (pi), both IL-10 and TGF-ß1 prevented the development of acute EAE in Lewis rats.

When IL-10 or TGF-ß1 was administered by the nasal route from day 5 to day 12 pi, both IL-10 and TGF-ß1 failed to influence clinical EAE.

The inhibition of clinical EAE severity in IL-10-prevented rats was associated with reduced proliferation, IFN-γ mRNA expression, and IFN-γ secretion, while proliferation as well as IFN-γ mRNA expression and secretion were augmented in TGF-ß1-prevented rats.

TGF-ß1-prevented rats exhibited high levels of NO production by DC, which may mediate Apoptosis of CD4⁺ T-Cells and of the DC themselves.

For prevention, both IL-10 and TGF-ß1 inhibited infiltration of CD4⁺ T-Cells within the CNS, but neither IL-10 nor TGF-ß1 induced Immune deviation from Th1 to Th2.

Expression of IL-4 mRNA was not altered in IL-10- and TGF-ß1-prevented rats. These results demonstrate that IL-10 and TGF-ß administration by the nasal route can prevent the development of acute EAE, but by different mechanisms.

The findings in rats with ongoing EAE have implications for the clinical application of Cytokine treatment in AutoImmune Diseases.

Dysregulation of InterLeukin-2 (IL-2), the prototypical T-Cell growth factor and ImmunoRegulatory Cytokine, may modify self-tolerance and predisposition to AutoImmunity.

The available literature suggested that IL-2 could be hypothesized to either propagate or inhibit the development AutoImmune DeMyelinating Disorders of the Central Nervous System such as Multiple Sclerosis.

Thus, the present study sought to test these competing hypotheses by examining whether disrupting one or both IL-2 Gene Alleles would render mice more or less vulnerable to Experimental AutoImmune EncephaloMyelitis (EAE).

Myelin Oligodendrocyte Glycoprotein was used to induce EAE in C57BL/6-IL-2(-/-) knockout, C57BL/6-IL-2(+/-) heterozygote and C57BL/6-IL-2(+/+) wild-type mice.

All of the wild-type and heterozygote mice developed signs of EAE compared with only 23% of the IL-2 knockout mice.

HistoPathological examination of Lumbar Spinal Cord sections confirmed that SubPial PeriVascular inflammatory infiltrates found in wild-type and heterozygote mice were absent in the unaffected IL-2 knockout mice.

These data demonstrate that vulnerability to EAE is markedly reduced in C57BL/6 mice lacking IL-2, and suggest that this Cytokine may play a critical role in AutoImmune processes of the Central Nervous System.

The primary pathological mechanisms in Stroke and Multiple Sclerosis (MS) are very different but in both diseases, Impairment may arise from a final common pathway of Axonal damage.

We aimed to examine the relationship between motor impairment, Magnetization Transfer Ratio (MTR) (an index of DeMyelination), and N-AcetylAspartate (NAA) loss (an index of Axonal Injury) localized to the Descending Motor Pathways in Stroke and MS.

Twelve patients between 1 and 10 months after first ischaemic Stroke causing a Motor Deficit and 12 patients with stable MS with asymmetric Motor Deficit were examined.

T₂-weighted imaging of the Brain together with MTR and proton (Voxel (volume element) 1.5 x 2 x 2 cm(3)) MRS localized to the Posterior Limb of the Internal Capsule were performed and correlated to a composite Motor Deficit score.

MTR and NAA in the Internal Capsule were reduced in both Stroke and MS patients compared to controls. NAA loss correlated with Motor Deficit score in both Stroke and MS (p < 0.001 and p = 0.04, respectively).

Correlations were seen between MTR and Motor Deficit (p < 0.001) MTR and NAA loss (p < 0.001) in Stroke patients but not in MS patients.

Axonal injury in the descending motor tracts would appear to be an important determinant of motor impairment in both Stroke and MS.

In Stroke, MTR measures of DeMyelination are closely related to Axonal damage and thus also correlate with Motor Deficit.