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.
Quality Of Life And Multiple Sclerosis: Validation Of The French Version Of The MSQOF Self-Questionnaire (SEP-59)
Vernay D, Gerbaud L, Biolay S, Coste J, Debourse J, Aufauvre D, Beneton C, Colamarino R, Glanddier PY, Dordain G, Clavelou P
Rev Neurol (Paris) 2000;156(3):247-263
Federation de Neurologie
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The translation into French has an addition of five items, because we kept the MS specific items of an earlier unpublished form.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.
The Complexicity Of Cytokine Treatment In Ongoing EAE Induced With MBP Peptide 68-86 In Lewis Rats
Xu LY, Ishikawa M, Huang YM, Levi M, van der Meide PH, Wahren B, Link H, Xiao BG
Clin Immunol 2000 Apr;95(1 Pt 1):70-8
Karolinska Institute, Division of Neurology, Huddinge Univ Hospital, Stockholm, Sweden
PMID# 10794434; UI# 20252408
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.
InterLeukin-2 Gene Deletion Produces A Robust Reduction In Susceptibility To Experimental AutoImmune EncephaloMyelitis In C57BL/6 Mice
Petitto JM, Streit WJ, Huang Z, Butfiloski E, Schiffenbauer J
NeuroSci Lett 2000 May 5;285(1):66-70
UF Brain Institute, Dept of Psychiatry, Box 100256,
Univ of Florida College of Medicine, Gainesville, USA
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.
Correlating Magnetic Resonance Imaging Markers Of Axonal Injury And DeMyelination In Motor Impairment Secondary To Stroke And Multiple Sclerosis
Pendleburyab ST, Lee MA, Blamire AM, Styles P, Matthews PM
Magn Reson Imaging 2000 May;18(4):369-78
Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), John Radcliffe Hospital, Oxford, UK
PMID# 10788713; UI# 20251109
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.
However in MS, MTR measures of DeMyelination do not correlate with NAA loss or motor deficit suggesting that DeMyelination and Gliosis may occur independently of Axonal damage and are less closely linked with functional impairment.