H Wiendl

Publications of H Wiendl

• Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort.

  Authors: A K Trampe, C Hemmelmann, A Stroet, A Haghikia, K Hellwig, H Wiendl, S Goelz, A Ziegler, R Gold, A Chan

  Neurology. 05/2012;

  OBJECTIVE:To investigate the rate of seropositivity of anti-JC virus (JCV) antibodies in a German multiple sclerosis (MS) cohort treated with natalizumab in the postmarketing setting and to assessOBJECTIVE:To investigate the rate of seropositivity of anti-JC virus (JCV) antibodies in a German multiple sclerosis (MS) cohort treated with natalizumab in the postmarketing setting and to assess anti-JCV serostatus in samples obtained before diagnosis of progressive multifocal leukoencephalopathy (PML). METHODS:This was a blinded, retrospective cross-sectional and longitudinal analysis for anti-JCV antibodies using a confirmatory 2-step ELISA on 2,782 blood samples obtained from 2,253 patients nationwide for routine testing for anti-natalizumab antibodies during open-label treatment between 2007 and 2010. RESULTS:Of the natalizumab-treated patients with MS, 58.8% tested positive for anti-JCV antibodies. The rate of seropositivity was higher in males and increased with age, with a plateau between age intervals 20-29 and 30-39 years. In longitudinal analyses, 19 of 194 (9.8%) patients converted from anti-JCV antibody-negative to seropositive status over 7.7 months; 4.7% reverted from antibody-positive to seronegative status over 7.9 months. Antibody levels, especially in the latter group, were low, indicating fluctuations around the lower cut point of the assay. Neither anti-JCV serostatus nor antibody levels were associated with immunosuppressive pretreatment, duration of natalizumab treatment, or anti-natalizumab antibodies. All samples obtained from 10 patients who developed PML were seropositive (13 samples before PML diagnosis [2.0-37.6 months]; 2 samples at diagnosis). Antibody levels in these samples were higher than those in samples from seropositive patients who did not develop PML. CONCLUSIONS:These data argue for the potential clinical utility of JCV serology for PML risk stratification. However, further investigations of fluctuations in serostatus and of antibody levels for a more precise understanding of the predictive value are warranted.

• Fatal PML associated with efalizumab therapy: Insights into integrin αLβ2 in JC virus control.

  Authors: N Schwab, J C Ulzheimer, R J Fox, T Schneider-Hohendorf, B C Kieseier, C M Monoranu, S M Staugaitis, W Welch, S Jilek, R A Du Pasquier, W Brück, K V Toyka, R M Ransohoff, H Wiendl

  Neurology. 02/2012; 78(7):458-67.

  Progressive multifocal leukoencephalopathy (PML) has become much more common with monoclonal antibody treatment for multiple sclerosis and other immune-mediated disorders. We report 2 patients withProgressive multifocal leukoencephalopathy (PML) has become much more common with monoclonal antibody treatment for multiple sclerosis and other immune-mediated disorders. We report 2 patients with severe psoriasis and fatal PML treated for ≥3 years with efalizumab, a neutralizing antibody to αLβ2-leukointegrin (LFA-1). In one patient, we conducted serial studies of peripheral blood and CSF including analyses of leukocyte phenotypes, migration ex vivo, and CDR3 spectratypes with controls coming from HIV-infected patients with PML. Extensive pathologic and histologic analysis was done on autopsy CNS tissue of both patients. Both patients developed progressive cognitive and motor deficits, and JC virus was identified in CSF. Despite treatment including plasma exchange (PE) and signs of immune reconstitution, both died of PML 2 and 6 months after disease onset. Neuropathologic examination confirmed PML. Efalizumab treatment was associated with reduced transendothelial migration by peripheral T cells in vitro. As expression levels of LFA-1 on peripheral T cells gradually rose after PE, in vitro migration increased. Peripheral and CSF T-cell spectratyping showed CD8+ T-cell clonal expansion but blunted activation, which was restored after PE. From these data we propose that inhibition of peripheral and intrathecal T-cell activation and suppression of CNS effector-phase migration both characterize efalizumab-associated PML. LFA-1 may be a crucial factor in homeostatic JC virus control.

• CD8+ T-cell immunity in chronic inflammatory demyelinating polyradiculoneuropathy.

  Authors: T Schneider-Hohendorf, N Schwab, N Uçeyler, K Göbel, C Sommer, H Wiendl

  Neurology. 02/2012; 78(6):402-8.

  Chronic inflammatory demyelinating polyradiculopathy (CIDP) is a common, but often misdiagnosed disease of the peripheral nervous system with assumed autoimmune pathogenesis. While current conceptsChronic inflammatory demyelinating polyradiculopathy (CIDP) is a common, but often misdiagnosed disease of the peripheral nervous system with assumed autoimmune pathogenesis. While current concepts of CIDP postulate a pathogenetic role of B cells and (auto)antibodies, the relevance of CD8 T cells present in the biopsies is still elusive. Thus, we asked whether nervous tissue infiltrating and blood-derived lymphocytes in CIDP are clonally expanded to evaluate the involvement of T cells in the pathogenesis of the disease. We characterized the clonal composition of the T-cell receptor repertoire in sural nerve biopsies (n = 25) and matching peripheral blood (n = 12) of patients with CIDP using PCR-based CDR3 spectratyping and subsequent DNA sequencing. As controls we used inflammatory myopathies (dermatomyositis, inclusion body myositis) and nonpathologic control biopsies. Immunohistochemistry was employed to visualize expanded CD8+ T-cell populations in sural nerve biopsies. In contrast to controls, T cells in CIDP biopsies showed strong monoclonal and oligoclonal restrictions in their T-cell receptor repertoire. Strikingly, clonal expansions found in the biopsies were reflected in the CD8+ T-cell pool of patients' peripheral blood. Clones overlapping between blood and biopsy could be confirmed by CDR3 sequencing. Finally, the predominance of expanded nerve-infiltrating CD8+ T-cell clones was visualized by immunohistochemistry. Together, these data provide strong evidence for an antigen-driven, major histocompatibility complex class I restricted, CD8+ T-cell-mediated attack against peripheral nerve tissue components contributing to the pathogenesis of CIDP.

• Evaluation of soluble HLA-G as a biomarker for multiple sclerosis.

  Authors: A Waschbisch, R Sandbrink, H-P Hartung, L Kappos, S Schwab, C Pohl, H Wiendl

  Neurology. 08/2011; 77(6):596-8.

• [Risk stratification of progressive multifocal leukoencephalopathy under natalizumab: recommendations for JC virus serology].

  Authors: C Warnke, O Adams, H P Hartung, R Gold, B Hemmer, R Hohlfeld, M Stangel, F Zipp, H Wiendl, B C Kieseier

  Der Nervenarzt. 06/2011; 82(10):1314-9.

  JC virus (JCV)-associated progressive multifocal leukoencephalopathy (PML) represents a rare but serious side effect of natalizumab (Tysabri®) in the treatment of patients with relapsing forms ofJC virus (JCV)-associated progressive multifocal leukoencephalopathy (PML) represents a rare but serious side effect of natalizumab (Tysabri®) in the treatment of patients with relapsing forms of multiple sclerosis (MS). Two factors that may increase the risk of PML have been identified: treatment duration beyond 24 months and prior immunosuppressive therapy. Recently determination of anti-JCV antibodies mirroring JCV infection has allowed a third factor to be added to this list, and a positive serological test has been included as a risk factor on the label of natalizumab. Clearly, JCV serology represents a tool for PML risk stratification in MS patients treated with natalizumab. However, current data as well as the experimental development of the underlying assay have not been validated by an independent laboratory.The present article discusses possibilities and challenges of this assay and, based on our present knowledge, provides recommendations for the clinical implementation in daily practice.

• [Pregabalin and gabapentin in multiple sclerosis: clinical experiences and therapeutic implications].

  Authors: S Bittner, K Höhn, K Göbel, C Kleinschnitz, H Wiendl, S G Meuth

  Der Nervenarzt. 06/2011; 82(10):1273-80.

  Due to a plethora of additional symptoms patients with multiple sclerosis (MS) receive symptomatic treatment besides disease-modifying therapies. Among the substances which are commonly used are ionDue to a plethora of additional symptoms patients with multiple sclerosis (MS) receive symptomatic treatment besides disease-modifying therapies. Among the substances which are commonly used are ion channel modulators (e. g. pregabalin, gabapentin, carbamazepine). The aim of this study was to investigate the use of these drugs in clinical practice in a larger patient cohort. Data from 533 MS patients [439 without and 94 patients with add-on therapy (treatment group)] were evaluated retrospectively. All patients received a detailed neurological examination including evaluation of EDSS scores. Pregabalin and gabapentin are used most commonly. Abnormal sensations are the most frequent reason for therapy initiation. Patients with higher EDSS values and/or under mitoxantrone treatment most frequently receive additional therapy. So far, it is not known whether the investigated agents exert a beneficial influence on the disease course of MS itself beyond a mere symptomatic treatment. Further research efforts and clinical studies are necessary to address this question.

• [Diagnosis of multiple sclerosis 2010 revision of the McDonald criteria].

  Authors: L Klotz, R Gold, B Hemmer, T Korn, F Zipp, R Hohlfeld, B C Kieseier, H Wiendl

  Der Nervenarzt. 05/2011; 82(10):1302-9.

  In 2010, the second revision of the McDonald criteria for diagnosis of multiple sclerosis was proposed. Based on new evidence, the imaging criteria for demonstration of dissemination of centralIn 2010, the second revision of the McDonald criteria for diagnosis of multiple sclerosis was proposed. Based on new evidence, the imaging criteria for demonstration of dissemination of central nervous system lesions in space and time have been simplified, which will allow broader application in a more uniform manner. In some circumstances, dissemination in space and time can be demonstrated in a single scan. The revision simplifies the criteria and allows accelerated diagnostic procedures while preserving their sensitivity and specificity. Additionally, the applicability across populations and in children is addressed.

• Highly reactive anti-myelin oligodendrocyte glycoprotein antibodies differentiate demyelinating diseases from viral encephalitis in children.

  Authors: P H Lalive, M G Häusler, H Maurey, Y Mikaeloff, M Tardieu, H Wiendl, M Schroeter, H P Hartung, B C Kieseier, T Menge

  Multiple sclerosis (Houndmills, Basingstoke, England). 01/2011; 17(3):297-302.

  Myelin oligodendrocyte glycoprotein (MOG) may be implicated in the immunopathogenesis of multiple sclerosis (MS) inducing demyelination in the animal model of MS. In adults reported anti-MOG antibodyMyelin oligodendrocyte glycoprotein (MOG) may be implicated in the immunopathogenesis of multiple sclerosis (MS) inducing demyelination in the animal model of MS. In adults reported anti-MOG antibody frequencies have been variable across a number of studies and can also be detected in controls. To measure antibodies against MOG in paediatric patients with demyelinating disorders of the central nervous system and in controls. Serum antibodies against MOG and myelin basic protein were measured by ELISA, flow cytometry (FACS) and in the liquid phase in 11 children with acute disseminated encephalomyelitis (ADEM), 22 children with MS, seven children with acute viral encephalitis and 13 healthy controls. The serostatus of Epstein-Barr virus (EBV) infections were assessed. Anti-MOG antibodies, measured either by ELISA or FACS were exclusively detected in children with demyelination. In ADEM these antibodies were highly reactive. Anti-MBP reactivity was detectable equally in all groups. The presence of either autoantibodies did not associate with EBV serostatus, age, gender or disease course. This study independently corroborates recently published results of seroprevalence and specificity of the assay. Due to their low sensitivity anti-MOG antibodies will not serve as disease-specific biomarkers, but could help to support the diagnosis of ADEM in difficult cases.

• [Progressive multifocal leukoencephalopathy under natalizumab. Initial possibilities for risk stratification?].

  Authors: C Warnke, O Adams, R Gold, H-P Hartung, R Hohlfeld, H Wiendl, B C Kieseier

  Der Nervenarzt. 01/2011; 82(4):475-80.

  Natalizumab (Tysabri®) is the first monoclonal antibody approved for the treatment of relapsing forms of multiple sclerosis (MS) but while treatment is highly efficient, it carries the risk ofNatalizumab (Tysabri®) is the first monoclonal antibody approved for the treatment of relapsing forms of multiple sclerosis (MS) but while treatment is highly efficient, it carries the risk of progressive multifocal leukoencephalopathy (PML). Based on reports of confirmed cases of PML, the risk of PML might increase beyond 24 months of treatment. Thus, attempts to stratify patients treated with natalizumab into those carrying higher or lower risk for developing PML are currently being undertaken. Among these strategies JC virus serology might potentially be the first tool available. As a large variety of methods have been published resulting in controversial results for JC virus seroprevalence, standardized testing will be mandatory when applying this method in clinical practice. In addition, risk management strategies for the seropositive majority of patients need to be redefined and optimized further.

• ["Chronic cerebrospinal venous insufficiency" and multiple sclerosis: critical analysis and first observation in an unselected cohort of MS patients].

  Authors: C Krogias, A Schröder, H Wiendl, R Hohlfeld, R Gold

  Der Nervenarzt. 04/2010; 81(6):740-6.

  Currently, the hypothesis that altered venous hemodynamics might play a causative role in the pathogenesis of multiple sclerosis (MS) is being controversially discussed. This new "venous hypothesis"Currently, the hypothesis that altered venous hemodynamics might play a causative role in the pathogenesis of multiple sclerosis (MS) is being controversially discussed. This new "venous hypothesis" postulates that obstructions of the cervical venous system cause an increased pressure of the intracranial venous system and that in turn intracranial congestion disintegrates the blood-brain barrier initiating the inflammatory process in MS.The "venous hypothesis" is analyzed and evaluated with regard to the following aspects: first concerning the validity of published data, second with regard to the plausibility in view of the currently approved pathogenetic model of MS, and third with regard to the compatibility with preliminary neurosonological findings in a small but unselected cohort of patients at our department.The authors conclude that the "chronic cerebrospinal venous insufficiency (CCSVI)" cannot represent the exclusive pathogenetic factor in the pathogenesis of MS. In our cohort, only 20% of the patients fulfilled the required neurosonological features of CCSVI. So far, the pathogenetic relevance of these findings remains speculative. Thus, based on the current scientific position we cannot justify invasive "therapeutic" approaches, especially if they are performed outside of clinical trials.

• [Therapeutic monoclonal antibodies in clinical neurology].

  Authors: M Buttmann, H Wiendl

  Der Nervenarzt. 03/2010; 81(6):753-64; quiz 765-6.

  Recombinant monoclonal antibodies break new ground in the treatment of immune-mediated nerve and muscle disorders but also of neurodegenerative diseases, in the field of neuro-oncology and in painRecombinant monoclonal antibodies break new ground in the treatment of immune-mediated nerve and muscle disorders but also of neurodegenerative diseases, in the field of neuro-oncology and in pain therapy, as they allow molecular targeting of defined cell populations or key pathophysiological molecules. However, safety risks might accompany a high efficacy. Basic understanding of this increasingly important class of agents and a steady update of knowledge, in particular on safety aspects, are therefore key requirements for responsible use based on an individual benefit-risk assessment.

• Interferon beta treatment does not induce organ-specific autoantibodies in multiple sclerosis.

  Authors: T Menge, N C Schloot, M Schott, B Hemmer, H Wiendl, M Roden, H P Hartung, B C Kieseier

  Neurology. 09/2009; 73(11):900-2.

• Dose-dependent melanonychia by mitoxantrone.

  Authors: C Reinsberger, Sg Meuth, H Wiendl

  Multiple sclerosis (Houndmills, Basingstoke, England). 08/2009;

  We report an unusual case of a 43-year old female patient suffering from multiple sclerosis, who was treated with mitoxantrone. Few weeks after treatment initiation a hyperpigmentation of theWe report an unusual case of a 43-year old female patient suffering from multiple sclerosis, who was treated with mitoxantrone. Few weeks after treatment initiation a hyperpigmentation of the patient's left thumb and index was noted. Following dose-reduction (from 12 to 10 mg/m(2)) and over the further course of mitoxantrone treatment the discoloration slightly faded. Although mitoxantrone is known to cause hyperpigmentation of various tissues this is the first report of melanonychia without hyperpigmentation of other tissue. Albeit speculative, pathogenesis of selective melanonychia by mitoxantrone could involve selective activation of nail matrix melanocytes or endocrine disturbances involving melanocyte stimulating hormone.

• [Cerebral and spinal MRI examination in patients with clinically isolated syndrome and definite multiple sclerosis]

  Authors: M Sailer, F Fazekas, A Gass, L Kappos, E W Radue, P Rieckmann, K Toyka, H Wiendl, M Bendszus

  RöFo : Fortschritte auf dem Gebiete der Röntgenstrahlen und der Nuklearmedizin. 12/2008; 180(11):994-1001.

  PURPOSE: Magnetic resonance imaging (MRI) has become a valuable tool for diagnosing and monitoring multiple sclerosis (MS). The high sensitivity for the detection of hyperintense lesions in TPURPOSE: Magnetic resonance imaging (MRI) has become a valuable tool for diagnosing and monitoring multiple sclerosis (MS). The high sensitivity for the detection of hyperintense lesions in T 2-weighted scans contributes substantially to diagnosis. The initial lesion number or lesion volume stands for an increased probability of further accumulation of lesion burden, an earlier conversion to clinically definite MS and progression of disability in the next 5 - 15 years. This diagnostic and prognostic information gained from MRI early in the disease course lead in 2001 to a revision of the diagnostic criteria. MATERIALS AND METHODS: For the first time MRI criteria were defined in addition to the clinical and paraclinical criteria using the clinical terms for dissemination with respect to space and time. In particular, the defined MRI criteria are based on lesion number and location, the appearance of new lesions and lesion enhancement using contrast agent. RESULTS: Reliable detection and description of older and new lesions in the disease course by MRI represents subclinical disease activity which can substitute the clinical confirmation of a relapse leading to an earlier diagnosis. This places importance on the assessment of the subclinical disease activity in sequential MR scans requiring a standardized and reproducible approach to minimize variability despite different MR scanners. CONCLUSION: This review provides an updated proposal for the approach and management of cranial and spinal MR scans in patients with MS. We describe the influence of variables which cannot be standardized (scanner, field strength, manufacturer and software) and outline potential pitfalls of clinical MR imaging in MS resulting from a non-standardized approach. This updated proposal for slice positioning, sequences and documentation is a result of a consensus process targeting systematic and standardized use in clinical MR evaluations of MS.

• [Multiple sclerosis - a channelopathy? : Targeting ion channels and transporters in inflammatory neurodegeneration.]

  Authors: S G Meuth, N Melzer, C Kleinschnitz, T Budde, H Wiendl

  Der Nervenarzt. 12/2008;

  Multiple sclerosis (MS) has traditionally been regarded as an inflammatory demyelinating disorder of the CNS in which clinical symptoms result from axon conduction block caused by myelin degradation.Multiple sclerosis (MS) has traditionally been regarded as an inflammatory demyelinating disorder of the CNS in which clinical symptoms result from axon conduction block caused by myelin degradation. However, typical accumulation of permanent neurological deficits during the clinical course of MS cannot be explained solely by de- and remyelinating processes. It is considered to be rather due to neuronal degeneration, for which several reasons could be identified depending on the state of the disease. First, neurons and their axons can be damaged by infiltrating lymphocytes and macrophages either directly by cell-to-cell contact or by the release of harmful mediators such as nitric oxide or glutamate. Second, indirect injury to neurons and axons may occur through the loss of trophic support by neighbouring oligodendrocytes due to destruction of both the myelin sheath and the oligodendrocyte itself. Third, redistribution of certain voltage- and ligand-gated ion channels and transporters along naked demyelinated axons restores axonal conduction but also leads to excessive spatially restricted electrical activity of the axonal membrane, intracellular calcium accumulation, impairment of mitochondrial function, and subsequent neuronal degeneration. The neuroprotective potential of pharmacological modulation of these channels and transporters using already approved drugs has been demonstrated in several animal studies, is the subject of current clinical trials and will be the topic of this review.

• Basic and escalating immunomodulatory treatments in multiple sclerosis: Current therapeutic recommendations.

  Authors: H Wiendl, K V Toyka, P Rieckmann, R Gold, H P Hartung, R Hohlfeld

  Journal of neurology. 11/2008; 255(10):1449-63.

  This review updates and extends earlier Consensus Reports related to current basic and escalating immunomodulatory treatments in multiple sclerosis (MS). The recent literature has been extracted forThis review updates and extends earlier Consensus Reports related to current basic and escalating immunomodulatory treatments in multiple sclerosis (MS). The recent literature has been extracted for new evidence from randomized controlled trials, open treatment studies and reported expert opinion, both in original articles and reviews, and evaluates indications and safety issues based on published data. After data extraction from published full length publications and critically weighing the evidence and potential impact of the data, the review has been drafted and circulated within the National MS Societies and the European MS Platform to reach consensus within a very large group of European experts, combining evidence-based criteria and expert opinion where evidence is still incomplete. The review also outlines a few areas of controversy and delineates the need for future research.

• [Progressive multifocal leukoencephalopathy and rheumatic disease.]

  Authors: C Kneitz, H Wiendl

  Zeitschrift für Rheumatologie. 08/2008; 67(4):290-4.

  Progressive multifocal leukoencephalopathy (PML) is a rare but often fatal demyelinating disease of the central nervous system induced by the JC virus. It mainly occurs in immunocompromised patients.Progressive multifocal leukoencephalopathy (PML) is a rare but often fatal demyelinating disease of the central nervous system induced by the JC virus. It mainly occurs in immunocompromised patients. Growing interest in rheumatology has arisen from reports of patients with rheumatic diseases suffering from PML. A direct relationship to rheumatologic disease itself, for example systemic lupus erythematosus, or to immunosuppressive therapy, is debated. Therefore, PML should be included in the differential diagnosis of non-specific neurologic symptoms and, if suspected, relevant diagnostic procedures (MRI, CSF analysis including virus-specific PCR, and possibly brain biopsy) need to be performed.

• Immunoregulatory factors in multiple sclerosis patients during and after pregnancy: relevance of natural killer cells.

  Authors: L Airas, M Saraste, S Rinta, I Elovaara, Y H Huang, H Wiendl

  Clinical and experimental immunology. 03/2008; 151(2):235-43.

  Multiple sclerosis (MS) ameliorates typically during pregnancy but after the delivery the relapse rate often increases. Our study was conducted to understand the immunoregulatory mechanismsMultiple sclerosis (MS) ameliorates typically during pregnancy but after the delivery the relapse rate often increases. Our study was conducted to understand the immunoregulatory mechanisms accompanying this phenomenon. MS patients were followed-up prospectively during pregnancy and 6 months postpartum, with immunological characterization of the peripheral blood. Groups of age- and parity-matched healthy pregnant women, and age- and sex-matched non-pregnant women and non-pregnant MS patients were studied as controls. In our patient cohort, the annualized relapse rate was 1.0 +/- 1.0 relapses/woman/year (mean +/- standard deviation) during the year before pregnancy, but dropped to 0.2 +/- 0.9 during the third trimester (P = 0.02). After the delivery the relapse rate increased again to 1.4 +/- 1.9 (1-3 months postpartum versus third trimester P = 0.003). While percentages of peripheral blood CD3, CD4, CD8 and CD19 immune cell subsets were unchanged over the observation period, reduced disease activity during the last trimester was associated with a significant increase in the percentage of circulating CD56(bright) natural killer (NK) cells. Simultaneously, the proportion of circulating CD56(dim) NK cells was clearly reduced. No alteration was noted in CD4+ CD25(high) forkhead box P3+ regulatory T cells. Production of interferon-gamma by peripheral blood lymphocytes was down-regulated significantly during pregnancy in comparison to the postpartum period, resulting in an increased T helper type 2 (Th2) : Th1 ratio during pregnancy. In conclusion, pregnant state in MS patients is characterized by an increase in the percentage of CD56(bright) NK cells and by enhanced Th2 type cytokine secretion. Our findings suggest a potential role for CD56(bright) regulatory NK cells in the control of autoimmune inflammation during pregnancy in MS.

• Clonal expansions of pathogenic CD8+ effector cells in the CNS of myelin mutant mice.

  Authors: C Leder, N. Schwab, C W Ip, A Kroner, K A Nave, K. Dornmair, R Martini, H Wiendl

  Molecular and cellular neurosciences. 12/2007; 36(3):416-24.

  Tissue damage in the CNS is critically influenced by the adaptive immune system. Primary oligodendrocyte damage (by overexpression of PLP) leads to low-grade inflammation of high pathological impact,Tissue damage in the CNS is critically influenced by the adaptive immune system. Primary oligodendrocyte damage (by overexpression of PLP) leads to low-grade inflammation of high pathological impact, which is mediated by CD8+ T cells. To yield further insight into pathogenesis and nature of immune responses in myelin mutated mice, we here apply a detailed immunological characterization of CD8+ T cells in PLP-transgenic and aged wild type mice. We provide evidence that T effector cells accumulate in the CNS of PLP-transgenic and wild-type mice and show a higher level of activation in mutant mice, indicated by surface markers and clonal expansions, as demonstrated by T cell receptor CDR3-spectratype analysis. Vbeta-Jbeta similarities suggest specificity against a common antigen, albeit we could not find specific responses against myelin-antigen-derived peptides. The association of primary oligodendrocyte damage with secondary expansions of pathogenic cells underlines the role of adaptive immune reactions in neurodegenerative and neuroinflammatory diseases.

• Treosulfan impedes the migration of immunocompetent cells.

  Authors: T Kopadze, T Dehmel, H A Mylius, H P Hartung, H Wiendl, B C Kieseier

  Journal of neurology. 11/2007; 254(10):1457-8.