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T helper type 2 like cytokine responses to peptides from P0 and P2 myelin proteins during the recovery phase of Guillain-Barré syndrome
Linköping University, Department of Neuroscience and Locomotion, Neurology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Transfusion Medicine and Clinical Immunology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0002-3993-9985
Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
Department of Neurology, County Hospital, Örebro, Sweden.
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1997 (English)In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 153, no 1, 54-60 p.Article in journal (Refereed) Published
Abstract [en]

T-lymphocytes are probably involved in the pathogenesis of Guillain-Barré syndrome (GBS). T-helper-1 (Th1) cytokines activate macrophages and induce a delayed type hypersensitivity (DTH) inflammatory response, consistent with the morphology of the demyelination in GBS. Th2 cytokines encourage antibody production and downregulate Th1 responses. To study the Th1/Th2 cytokines in relation to the clinical course of GBS an ELISPOT method for determination of single cells secreting interferon-γ, IFN-γ (Th1) or interleukin-4, IL-4 (Th2) was used. We serially investigated antigen-induced cytokine secretion from circulating T-cells stimulated with human peptides from the P0 and P2 proteins in seven patients and compared to results from seven serially investigated healthy controls. Most patients (five of seven) showed IL-4 responses during the plateau- or recovery-phase as compared to controls. One patient with a prolonged disease course, on the other hand, had an IFN-γ dominated reactivity. We suggest that the IL-4 responses are beneficial in GBS, and may have a role in terminating the disease process in this self-limiting inflammatory disease.

Place, publisher, year, edition, pages
1997. Vol. 153, no 1, 54-60 p.
Keyword [en]
Guillain-Barré syndrome, Myelin, P0, P2, T cells, IFN-γ, IL-4
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-80193DOI: 10.1016/S0022-510X(97)00178-0OAI: diva2:546099
Available from: 2012-08-22 Created: 2012-08-22 Last updated: 2013-08-29Bibliographically approved
In thesis
1. Studies on T cells and cytokines in Guillain-Barré syndrome and experimental allergic neuritis
Open this publication in new window or tab >>Studies on T cells and cytokines in Guillain-Barré syndrome and experimental allergic neuritis
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Guillain-Barrésyndrome (GBS) is an inflammatory disease of peripheral nerves, characterised by muscle weakness. The nerves are attacked and destroyed by the immune system. The symptoms usually progress over a few weeks and many patients become severely disabled. However, in contrast to many other organspecific autoimmune diseases, GBS is self-limiting and most patients recover. Individuals of all ages can be affected. The incidence is about 1/100 000 per year. An infection often precedes the onset of neurological symptoms and probably triggers the immune-mediated attack.

Activation of T cells and the resulting release of cytokines are decisive for the regulation of antigen-specific inflammation. Different cytokine patterns promote different types of responses. Interferon-y (lFN-γ) has a key role in Th type 1 responses, and is thought to be a driving force in many organ-specific autoimmune diseases. Interleukin-4 (IL-4) promotes Th type 2 responses, characterised by the production of certain antibodies and activation of mastcells and eosinophils. Th type 1 and Th type 2 responses down-regulate one another and the balance between them is important for the immune homeostasis. TGF-ß is an important cytokine with strong down-regulatory properties.

Flow cytometry studies showed that circulating T cells were activated in patients with GBS as determined by expression of HLA-DR on T cells, increased proportion of activated memory phenotype (CD4+CD29+), and decreased proportion of naive phenotype (CD4+CD45RA+). A sensitive Ell-spot method was used to determine cytokine secretion from circulating mononuclear cells with or without stimulation with immunogenic peptides from myelin proteins P2 and PO. Both spontaneous and myelin-specific cytokine secretion were increased in patients compared with controls. Increased numbers of myelin-specific cells secreting IL-4 and TGF-ß were found in the majority of the patients, indicating a Th2 type and down-regulatory cytokine profile, in line with the self-limiting character of the disease.

An animal model of GBS, experimental allergic neuritis (EAN), is known to be inducible by myelin-specific T cells, supporting the pathogenetic role of T cells. A Th1 deviated, IFN-y-producing cell population from EAN, was in vitro stimulated with autoantigen and IL-4, thereby obtaining a Th2 cytokine profile. These myelin-specific cells were subsequently transferred to rats with EAN, and were found to ameliorate the disease course.

In conclusion, Circulating T cells are activated in patients with GBS. Most patients have myelin-specific T cells that mainly secrete down-regulatory cytokines such as IL-4 and TGF-ß, which probably have a beneficial role in regulating the disease process. In vitro deviation of myelin-specific T cells into Th2 phenotype and subsequent transfer of these cells ameliorated the disease course in EAN.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2001. 62 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 704
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-28074 (URN)12838 (Local ID)91-7373-151-X (ISBN)12838 (Archive number)12838 (OAI)
Public defence
2001-12-06, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-08-22Bibliographically approved

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Dahle, CharlotteEkerfelt, ChristinaVrethem, MagnusErnerudh, Jan
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NeurologyDepartment of Transfusion Medicine and Clinical ImmunologyFaculty of Health Sciences
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