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  • 1. Bracci-Laudiero, Luisa
    et al.
    Aloe, Luigi
    Buanne, Pasquale
    Finn, Anja
    Stenfors, Carina
    Vigneti, Eliana
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Lundeberg, Thomas
    NGF modulates CGRP synthesis in human B-lymphocytes: A possible anti-inflammatory action of NGF?2002In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 123, no 1-2, p. 58-65Article in journal (Refereed)
    Abstract [en]

    We investigated whether the sensory neuropeptide, calcitonin gene-related peptide (CGRP), could be synthesised by human lymphocytes. Our results indicate that in activated B-cells, there is a strong expression of CGRP gene transcripts, which is almost absent in resting cells. Since B-cells autocrinally produce NGF, the neutralisation of endogenous NGF by anti-NGF antibodies resulted in a marked reduction in CGRP expression in both resting and activated B-cells. Thus, NGF appears to directly affect the synthesis of CGRP in B-cells as in sensory neurons. By regulating CGRP synthesis in lymphocytes and neuronal cells, NGF can influence the intensity and duration of the immune response. ⌐ 2002 Elsevier Science B.V. All rights reserved.

  • 2.
    Dahle, Charlotte
    et al.
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Vrethem, Magnus
    Linköping University, Department of Neuroscience and Locomotion, Neurology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    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.
    T lymphocyte subset abnormalities in peripheral blood from patients with the Guillain-Barré syndrome1994In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 53, no 2, p. 219-225Article in journal (Refereed)
    Abstract [en]

    T lymphocytes are probably of pathogenic importance in many autoimmune diseases. Recently, deviations of circulating T-helper (CD4+) subpopulations have been noticed. Blood samples from 12 patients with Guillain-Barré syndrome (GBS) were studied with flow cytometry during their disease to define circulating T cell populations. The proportion of T-helper cells (CD4+) was decreased (mean value 41±15%, P = 0.01) and the proportion of T cytotoxic/suppressor cells (CD8+) was increased (35±18%, P = 0.0006) as compared to the control group of healthy blood donors (47±8% and 26±7% respectively). The CD4+ population is divided into the helper/inducer (CD4+ CD29+) and suppressor/inducer (CD4+ CD45RA+) subsets. which normally are equally distributed (mean values in our control group were 45±15% and 44±15%, respectively). In patients with GBS, the helper/inducer (CD4+ CD29+) subset was increased (54±10%, P = 0.05) and the suppressor/inducer (CD4+ CD45RA+) subset was decreased (31±9, P = 0.005) compared to the controls. The proportion of activated HLA-DR-expressing T cells was increased (7±8%, P = 0.005) as compared to control (3±3%). The total proportions of T cells (CD2+), B cells (CD19+) and natural killer (NK) cells (CD56+) were similar in pateints and controls. The CD4+ and CD8+ populations, as well as the activated HLA-DR+ T cells, normalized during the disease course. The derivations within the CD4+ population also tended to normalize, but even at follow up after 6–33 (mean 23) months, some abnormalities remained. In conclusion, we confirm previous reports of T cell activation in peripheral blood from patients with GBS. A new finding is the derivation of T helper subpopulations with an increased helper/inducer (CD4+ CD29+) subset and a decreased suppressor/inducer (CD4+ CD45RA+) subset, which indicates a possible autoimmune character of GBS.

  • 3.
    Ekerfelt, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Jarefors, Sara
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Tynngard, N
    Hedlund, M
    Sander, B
    Bergström, S
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Phenotypes indicating cytolytic properties of Borrelia-specific interferon-? secreting cells in chronic Lyme neuroborreliosis2003In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 145, no 1-2, p. 115-126Article in journal (Refereed)
    Abstract [en]

    The immuno-pathogenetic mechanisms underlying chronic Lyme neuroborreliosis are mainly unknown. Human Borrelia burgdorferi (Bb) infection is associated with Bb-specific secretion of interferon-? (IFN-?), which may be important for the elimination of Bb, but this may also cause tissue injury. In order to increase the understanding of the pathogenic mechanisms in chronic neuroborreliosis, we investigated which cell types that secrete IFN-?. Blood mononuclear cells from 13 patients with neuroborreliosis and/or acrodermatitis chronicum atrophicans were stimulated with Bb antigen and the phenotypes of the induced IFN-?-secreting cells were analyzed with three different approaches. Cells expressing CD8 or TCR?d, which both have cytolytic properties, were the main phenotypes of IFN-?-secreting cells, indicating that tissue injury in chronic neuroborreliosis may be mediated by cytotoxic cells.

  • 4.
    Grusell, Mattias
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases.
    Widhe, Mona
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ekerfelt, Christina
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Increased expression of the Th1-inducing cytokines interleukin-12 and interleukin-18 in cerebrospinal fluid but not in sera from patients with Lyme neuroborreliosis2002In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 131, no 1-2, p. 173-178Article in journal (Refereed)
    Abstract [en]

    Lyme neuroborreliosis is a complex disease with different clinical outcomes and where immunopathological mechanisms are probably involved. In this study, sera and cerebrospinal fluid (CSF) from 21 neuroborreliosis patients and 26 control patients were analyzed for the Th1-inducing cytokines, interleukin (IL)-12 and IL-18, and the Th2 associated, soluble CD30 (sCD30) by ELISA. The results showed an increased number of neuroborreliosis patients expressing IL-12 (p<0.05) and IL-18 (p<0.05) in the CSF when compared with the controls, but no indication of increased levels in the sera. Nor were there any differences regarding levels of sCD30 in the sera or the CSF, indicating a local Th1-generating milieu in the target organ of neuroborreliosis.

  • 5.
    Hallin, Elisabeth
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Mellergård, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurology. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Vrethem, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurology. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    In vitro Th2 deviation of myelin-specific peripheral blood lymphocytes from patients with multiple sclerosis2006In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 171, no 1-2, p. 156-162Article in journal (Refereed)
    Abstract [en]

    This study aimed at investigating if selective ex vivo immune deviation of myelin-specific cytokine secretion towards Th2 is possible in blood cells from patients with multiple sclerosis (MS). Interleukin (IL)-4 (Th2) and interferon-γ (Th1) secreting cells were recorded by ELISPOT in 13 MS patients. Deviation was successful in 10 patients. Interleukin-4 alone was most effective in inducing myelin-specific immune deviation in MS patients whereas IL-1 or IL-15 in combination with IL-4 did not improve the results. Further studies and improvements are needed before ex vivo immune deviation can be considered a potential treatment in patients with MS. © 2005 Elsevier B.V. All rights reserved.

  • 6.
    Henningsson, Anna J.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Department of Infectious Diseases, Ryhov County Hospital, Jönköping.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Sandholm, Kerstin
    Department of Chemistry and Biomedical Sciences, University of Kalmar, Kalmar.
    Carlsson, Sten-Anders
    Åland Borrelia Group, Åland Central Hospital, Finland.
    Granlund, Hans
    Åland Borrelia Group, Åland Central Hospital, Finland.
    Jansson, Christian
    Åland Borrelia Group, Åland Central Hospital, Finland.
    Nyman, Dag
    Åland Borrelia Group, Åland Central Hospital, Finland.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Nilsson Ekdahl, Kristina
    Department of Chemistry and Biomedical Sciences, University of Kalmar, Kalmar.
    Complement activation in Lyme neuroborreliosis - Increased levels of C1q and C3a in cerebrospinal fluid indicate complement activation in the CNS2007In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 183, no 01-Feb, p. 200-207Article in journal (Refereed)
    Abstract [en]

    A strong initial inflammatory response is important in neuroborreliosis. Since complement is a main player in early inflammation, we monitored the concentration and activation of complement in plasma and cerebrospinal fluid from 298 patients, of whom 23 were diagnosed with neuroborreliosis. Using sandwich ELISAs, we found significantly elevated levels of C1q, C4, C3, and C3a in cerebrospinal fluid, but not in plasma, in patients with neuroborreliosis. This finding indicates that complement plays a role in the human immune response in neuroborreliosis, that the immunologic process is compartmentalized to the CNS, and that complement activation may occur via the classical pathway.

  • 7.
    Keita, Asa V.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Stertman, Linda
    Uppsala University.
    Sun, Yi-Qian
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery .
    Larhed, Agneta
    Uppsala University.
    Sjoholm, Ingvar
    Uppsala University.
    Söderholm, Johan D
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Effects of chronic stress on the immune response to oral human serum albumin-conjugated starch microparticles in rats2007In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 183, no 01-Feb, p. 33-42Article in journal (Refereed)
    Abstract [en]

    Uptake of antigens and bacteria over the follicle-associated epithelium (FAE) is increased after chronic psychological stress. We investigated whether stress affects the immune response to particle-conjugated antigens taken up via the FAE. Rats were submitted to two 10-day periods of water avoidance stress and orally immunized during these periods. Stressed immunized rats displayed altered cell populations and a Th1-skewed immune response within the lymphoid follicles, together with enhanced delayed-type hypersensitivity. We conclude that chronic stress affects the cell-mediated immune response after oral immunization, which may have implications for the understanding of allergic and autoimmune diseases and development of oral vaccines. (c) 2006 Elsevier B.V. All rights reserved.

  • 8.
    Nordberg, Marika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Johansson, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases.
    Nyman, Dag
    Aland Central Hospital.
    Jansson, Christian
    Aland Central Hospital.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology.
    Cytotoxic mechanisms may play a role in the local immune response in the central nervous system in neuroborreliosis2011In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 232, no 1-2, p. 186-193Article in journal (Refereed)
    Abstract [en]

    Aiming to investigate the role of cytotoxic mechanisms in neuroborreliosis (NB), the cytokines IL-2, IL-7, IL-10, IL-12p70, IL-15, GM-CSF and the Th17-cytokine IL-17 were analyzed in cerebrospinal fluid (CSF) and plasma from NB-patients. NB-patients showed increased levels in CSF compared to controls of all analyzed cytokines except IL-15 but not in plasma. Blood lymphocytes from three NB-patients showed functional cytotoxicity in response to autologous Borrelia-infected macrophages. The findings support a role for cytotoxic mechanisms in the local immune response in NB and in addition suggest an increase of IL-17.

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