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OLSSON Tomas |
Tel.: +46-8-51776242
Fax: +46-8-51776248
e-mail: tomas.olsson@cmm.ki.se |
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Address |
Neuroimmunology Unit
CMM L8:04
Karolinska Hospital
S-17176 Stockholm |
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Research themes |
We dissect pathogenetic mechanisms and genes of relevance for inflammatory
damage to the central nervous system in multiple sclerosis (MS) and
experimental autoimmune encephalomyelitis (EAE) with a chronic MS-like
disease course induced with myelin oligodendrocyte glycoprotein (MOG) in
mice or rats. I. We have defined non-MHC genome regions regulating EAE
which now are subject : i) fine mapping, ii) comparative mapping in human
MS, iii) positional cloning attempts, and iv) functional analysis to
unravel mechanism of genetic regulation. II. We dissect mechanisms and
genes responsible for MHC class I, II and III region influences on MOG
EAE. III. MHC class II-MOG peptide tetramers will be constructed to study
mechanisms for T cell pathogenicity and spatiotemporal distribution during
natural disease and therapy. IV. The role of B cells/antibodies is studied
in a new mouse MOG EAE model using mice with targeted mutations in B cell
functionality genes.V. The role of inflammation for neuron damage is
dissected genetically and mechanistically in an experimental nerve damage
paradigm. VI. i) B and T cell autoimmunity to MOG and other relevant myelin
autoantigens is characterized in MS. ii) There are increased numbers of in
vivo activated lymphoid cells in MS patients. Their functions in disease
are now detailed. |
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Key words |
Genetics, Major Histocompatibility locus, autoimmunity, demylination, neurodegeneration, multiple sclerosis, experimental autoimmune encephalomyelitis, myelin oligodendrocyte glycoprotein. |
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Methods |
Keeping and breeding of approximately 30 different strains of rats, in
particular strains which are congenic for certain MHC and non-MHC genome
fragments regulating autoimmune neuroinflammation, as well as
intraregional recombinant strains. Extensive standard immunology
methodologies; antigen-induced proliferation, cytokine production
(ELISPOT), ELISA for antibodies and cytokines, intracellular cytokine
staining. Immunohistochemistry, molecular genotyping- gene mapping, gene
cloning, production of recombinant proteins, in situ hybridization for
mRNA /in situ-immunohistochemistry double labelling, FACS analysis and
sorting, standard PCR, TaqMan PCR, FPLC and SMART chromatography.
immunocytochemistry, animal models (EAE, EAMG, meningitis), stereotaxis |
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Composition of the research group |
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Tomas OLSSON |
Professor |
Dept med KS/Dept Neurol KS |
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Magnus Andersson |
Post doc/neurology clinician |
Dept med KS/Dept Neurol KS |
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Lou Brundin |
Ass.prof./neurology clinician |
Dept med KS/Dept Neurol KS |
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Robert A. Harris |
Ass.prof./Fo ass |
Dept med KS |
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Fredrik Piehl |
Post doc/neurology clinician Neurol KS |
Dept med KS/Dept |
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Anders Svenningsson |
Post doc/neurology clinician |
Dept med KS/Dept Neurol KS |
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Ingrid Dahlman |
Post doc |
Dept med KS |
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Erik Wallström |
PhD student |
Dept med KS |
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Sofia FRELAND |
Post doc |
Dept med KS |
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Anna LOBEL |
Post doc |
Dept med KS |
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Kathy de Graaf |
PhD student |
Dept med KS/Univ Tuebingen |
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Cecilia Lundberg |
PhD student |
Dept med KS |
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Olle Lidman |
PhD student |
Dept med KS |
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Saad Muhalab |
PhD student |
Dept med KS |
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Saana Eltayeb |
PhD student |
Dept med KS |
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Kristina Becanovic |
PhD student |
Dept med KS |
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Judit Wefer |
PhD student |
Dept med KS |
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Khairul Abdul Majid |
PhD student |
Dept med KS |
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Maja Jagodic |
PhD student |
Dept med KS |
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Maja Wållberg |
Project student |
Dept med KS |
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Mohsen Khademi |
Research assistant |
Dept med KS |
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Nabiha Basmaji |
Technician |
Dept med KS |
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Maine Blomstedt |
Technician |
Dept med KS |
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Ami Björkholm |
Secretary |
Dept med KS |
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Alexander Gielen |
Project student |
Dept med KS |
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Signe Hessler |
Project student |
Dept med KS |
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Recent publications
1. Weissert R, Wallström E, Storch M, Stefferl A, Lorentzen J, Lassmann H, Linington C, Olsson T: MHC haplotype-dependent regulation of MOG-induced EAE in rats. J Clin Invest 102:1265-1273, 1998.
2. Weissert R, Svenningsson A, Lobell A, de Graaf K, Andersson R, Olsson T: Molecular and genetic requirements for preferential recruitment of TCRBV8S2+ T cells in Lewis rat experimental autoimmune encephalomyelitis. J Immunol 160:681-690, 1998.
3. Lobell A, Weissert R, Olsson, T, Storch M, Svanholm C, de Graaf K, Lassmann H, Andersson R, Wigzell H. Vaccination with DNA encoding an immunodominant myelin basic protein peptide targeted to Fc gamma suppresses experimental autoimmune encephalomyelitis. J Exp Med 187:1543-1548, 1998.
4. Brundin L, Svenungsson E, Morcos E, Andersson M, Olsson T, Lundberg I, Wiklund P: CNS nitric oxide formation in cerebral SLE. Annals of Neurology 44 (4):704-6, 1998.
5. Wallström E, Khademi M, Andersson M, Weissert R, Linington C, Olsson T: Increased reactivity to myelin oligodendrocyte glycoprotein peptides and epitope mapping in HLA DR2(15)+ multiple sclerosis.Eur J Immunol 28:3329-3335, 1998.
6. Kjellén P, Issazadeh S, Olsson T, Holmdahl R: Genetic influence on disease course, cytokine responses and epitope spreading in relapsing experimental allergic encephalomyelitis. Int. Immunol 10:333-340, 1998.
7. Dahlman I, Lorentzen J, de Graaf K, Stefferl A, Linington C, Luthman H, Olsson T: Quantitative trait loci disposing for both experimental arthritis and encephalomyelitis in the DA rat; impact on severity of myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis and antibody isotype pattern. Eur J Immunol 28:2188-2196, 1998.
8. Storch MK, Stefferl A, Brehm U, Weissert R, Wallström E, Kerschensteiner M, Olsson T, Liningon C, Lassmann H: Autoimmunity to myelin oligodendrocyte glycoprotein in rats mimics the spectrum of multiple sclerosis pathology.
Brain Pathol 8:681-694, 1998.
9. Dahlman I, Jacobsson L, Glaser A, Lorentzen J, Andersson M, Luthman H, Olsson T. Genome-wide linkage analysis of chronic relapsing experimental autoimmune encephalomyelitis in the rat identifies a major susceptibility locus on chromosome 9. J Immunol 162:2581-2588, 1999.
10. Piehl F, Lundberg C, Khademi M, Bucht A, Dahlman I, Lorentzen J, Olsson T. Non-MHC gene regulation of nerve root injury induced spinal cord inflammation and neuron death. J Neuroimmunol 101:87-97, 1999.
11. de Graaf K, Weissert R, Kjellén P, Holmdahl R, Olsson R: Allelic variations in rat MHC class II binding of myelin basic protein peptides correlate with encephalitogenicity. Internat Immunol 11:1981-1987, 1999.
12. Dahlman I, Wallström E, Weissert R, Storch M, Kornek B, Jacobsson L, Linington C, Luthman H, Lassmann H, Olsson T. Linkage analysis of myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis in the rat identifies a locus controlling demyelination on chromosome 18. Hum Mol Gen 8:2183:2190, 1999.
13. Lobell A, Weissert R, Eltayeb S, Svanholm C, Olsson T, Wigzell H. Presence of CpG DNA and the local cytokine milieu determine the efficacy of suppressive DNA vaccination in experimental autoimmune encephalomyelitis. J Immunol 163:4754-4762, 1999.
14. Lidman O, Olsson T, Piehl F: Expression of nonclassical MHC class I (RT1-U) in certain neuronal populations of the central nervous system. Eur J Neuroscience 11:4468-4472, 1999.
15. Weissert R, Lobell A, de Graaf K L, Eltayeb S, Andersson R, Olsson T, Wigzell H: Protective DNA vaccination against organ-specific autoimmunity is highly specific and discriminates between single amino acid substitutions in the peptide autoantigen. PNAS 97:1689-1694, 2000. |
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