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11.
  • Johansson, Åsa, et al. (författare)
  • Non-Major Histocompatibility Complex dependent variations in lymphocyte activity between inbred mouse strains susceptible to various autoimmune diseases
  • 2000
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 52:1, s. 21-29
  • Tidskriftsartikel (refereegranskat)abstract
    • Transgenic techniques in inbred mouse strains are powerful tools to investigate the specific roles of genes in biological pathways and disease models. However, there is increasing concern over the influence of a variable genetic background in such experiments. To date there have been few investigations of the immunological differences between inbred mouse strains used in models of autoimmune diseases. Here we phenotyped lymph node cells and T-cell cytokine production in B10.Q (H2q), B10.RIII (H2r), C3H.Q (H2q), C3H. NB (H2p), NOD (H2g7), RIII/SJ (H2r) and DBA/1J (H2q) mice. We found several significant differences. The C3H strains and RIII/SJ lymph node cells had a high ratio of T cells/B cells (> 2 : 1) and a high ratio of CD4/CD8 positive cells (> 3 : 1), these strains are therefore denoted high T cell ratio (HiTR) strains. B10 strains and DBA/1, however, displayed an expansion of gammadeltaT cells after mitogen activation. T cells derived from C3H and DBA/1J strains produced more interleukin (IL)-4 than did T cells from B10 and NOD strains. DBA/1J and B10.Q showed a 10-fold increase in interferon (IFN)-gamma producing cells in the CD4+ T-cell population. Variation in the number of IL-2 and IFN-gamma producing T cells between the B10 major histocompatibility complex (MHC) congenic strains was the only difference possibly controlled by the MHC region. We conclude that non-MHC genes influence the numbers of T cells and B cells in lymph nodes, as well as IFN-gamma, IL-4 and IL-10 production by T cells.
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14.
  • Klint, Cecilia, et al. (författare)
  • Binding of immune complexes to erythrocyte CR1 (CD35): difference in requirement of classical pathway components and indication of alternative pathway-mediated binding in C2-deficiency
  • 2000
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 52:1, s. 103-108
  • Tidskriftsartikel (refereegranskat)abstract
    • Deficiency of complement components within the classical pathway is associated with increased risk for immune complex disease. However, C2-deficient individuals often have a mild disease and about 50% are healthy. To study the importance of the different components for immune complex clearance, bovine serum albumin (BSA)/anti-BSA complexes were opsonized in human serum and the binding to erythrocyte complement receptor type 1 (CR1, CD35) was measured in vitro. In C2-depleted serum the complexes were opsonized and bound to CR1 but the reaction needed a longer opsonization time than in normal human serum (NHS). In contrast, serum reagent lacking C1q, C4 or C3 did not promote binding in this assay system. We also demonstrated that elevated levels of factor B could restore binding of complexes to erythrocytes in C2-depleted serum via alternative pathway activation. These results indicate that in spite of lack of a complete classical pathway, C2-deficient individuals could retain some immune complex opsonizing activity via the alternative pathway. This finding could contribute to the understanding of differences in association between complement deficiency and immune-complex disease.
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16.
  • Lagerquist, Marie, et al. (författare)
  • 17Beta-estradiol expands IgA-producing B cells in mice deficient for the mu chain.
  • 2008
  • Ingår i: Scandinavian journal of immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 67:1, s. 12-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Oestrogen is not only a sex hormone but also an important regulator of the immune system. Expression of the heavy chain of IgM (mu) is essential for B-cell differentiation. However, a small number of IgA-positive B cells can be found in mice lacking the mu chain (muMT-/-). The aim of this study was to investigate the effects of oestrogen on this alternative B-cell pathway in muMT-/- mice. Our results clearly demonstrate that oestrogen increases the frequency of IgA-producing B cells in muMT-/- mice in both bone marrow and spleen cells. We also show that mature IgM-producing B cells are not required for oestrogen-mediated suppression of granulocyte-mediated inflammation or thymic involution. In conclusion, we demonstrate that 17beta-estradiol benzoate increases the frequency of IgA-producing B cells in muMT-/- mice, suggesting that oestrogen can influence the alternative B-cell pathway found in muMT-/- mice.
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17.
  • Larsson, L C, et al. (författare)
  • Neural tissue xenografting
  • 2000
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 52:3, s. 56-249
  • Tidskriftsartikel (refereegranskat)abstract
    • Neural transplantation may become an important treatment alternative for focal brain disorders. To date, the most successful grafts have been obtained in patients with Parkinson's disease. Completely normalized dopamine production and reduction of Parkinsonian symptoms have been demonstrated 10 years after grafting. However, the allogeneic donor tissue has to be obtained from induced abortions, and there are logistical difficulties, risks of infection, and ethical constraints limiting a wider clinical use. Xenografting is an alternative that could bridge these limitations if immunological rejection could be prevented. Pig embryonic neural tissue has been grafted to patients with Parkinson's disease, but no functional benefits have clinically been proven so far. The immune reactions to neural xenografts were incompletely characterized at the time of these early clinical trials, and it is likely that the treatments used were insufficient and that the grafts were rejected. In this article we will review new experiments addressing the immune responses against porcine neural tissue grafted to the adult brain, including the role of antibodies, complement, natural killer (NK) cells, lymphocytes, as well as the effects of immunosuppressive drugs and donor tissue modifications.
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18.
  • Larsson, Å., et al. (författare)
  • Ku protein and DNA strand breaks in lip glands of normal and primary Sjogren's syndrome subjects: Lack of correlation with apoptosis
  • 2001
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 54:3, s. 328-334
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim was to examine tissue expression of Ku protein in lower lip salivary gland (LSG) biopsies from cases of primary Sjogren's syndrome (SS) and from normal subjects. Methods: immunohistochemistry was used with antibodies to Ku70/86 and also Ki67, PCNA and p53. In addition, the Klenow method was applied in order to detect evidence of apoptosis. Sections of hyperplastic tonsil served as additional controls. Results: in normal controls, LSG acinar cells stained negatively whereas LSG excretory duct cell nuclei stained positively with Ku and Klenow and occasionally with PCNA but negatively with Ki67 and p53. In LSG focal sialadenitis of SS cases, some lymphocytic cells showed staining with Ku, Ki67, PCNA, Klenow and p53. In addition to duct cell Ku and Klenow as well as PCNA staining which was not much different from normals, a few ductal epithelial and also mononuclear cells stained with p53. In focal sialadenitis, some acinar cells showed staining with PCNA as well as with Klenow. Conclusions: our findings in LSG biopsies of SS cases added little to an increased understanding about the pathogenetic mechanisms in the development of focal sialadenitis in SS. However. in normal LSG. ductal epithelial but not acinar cells seem to express a constitutively specific Ku protein and Klenow profile, suggestive of DNA strand breaks but not clearly associated with ongoing apoptotic events. It may reflect an enhanced stress response, which may be pathogenetically important in the early events of focal sialadenitis development in primary Sjogren's syndrome.
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19.
  • Lavasani, Shahram, et al. (författare)
  • Monoclonal Antibody against T-Cell Receptor alphabeta Induces Self-Tolerance in Chronic Experimental Autoimmune Encephalomyelitis.
  • 2007
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 65:1, s. 39-47
  • Tidskriftsartikel (refereegranskat)abstract
    • The therapeutic effect of monoclonal antibody (H57-597 MoAb) against T-cell receptor (TCR) alpha beta has been investigated on MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE), as a model system for T-cell-mediated chronic inflammation in the central nervous system (CNS). Short-term administration of the anti-TCR alpha beta immediately after immunization protected the mice from EAE. Furthermore, anti-TCR alpha beta treatment on an established disease restored the self-tolerance which led to a complete remission of EAE and a dramatic reduction of inflammatory cells in the CNS, while treatment with control antibody (hamster IgG) was ineffective. The remission was durable and not associated with disappearance of autoreactive T cells as measured by persistence of MOG-reactive T-cell proliferation in vitro. However, MOG-reactive T cells from anti-TCR-treated animals produced significantly lower amounts of inflammatory TNF-alpha and IFN-gamma. In addition, while a transient deletion of CD4(+) and CD8(+) T cells was observed, a population of T cells expressing CD3, NK1.1 and CD69 (NKT cells) were expanding. By transfer of spleen cells from anti-TCR MoAb-treated animals, we could show that the tolerogenic capacity can be transferred to untreated recipients with EAE. The data indicate therapeutic effect of anti-TCR alpha beta MoAb (H57-597), which represents a promising approach in treatment of T-cell-mediated autoimmune diseases.
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20.
  • Lindstedt, Malin, et al. (författare)
  • Expression of CD137 (4-1BB) on Human Follicular Dendritic Cells
  • 2003
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 57:4, s. 305-310
  • Tidskriftsartikel (refereegranskat)abstract
    • Follicular dendritic cells (FDCs) are the antigen (Ag)-trapping accessory cells of the germinal centres (GCs), essential for the development of humoral immune responses and memory. FDCs reside in the microenvironment of secondary lymphoid tissue where Ag-activated B cells expand, and undergo isotype switching and affinity maturation prior to becoming memory B cells. In addition to delivering Ag, FDCs also provide potent nonspecific accessory signals to the B cells, which are important for the GC reaction. In this report, we show that human tonsilar FDCs express the costimulatory molecule CD137. Surface expression of CD137 on FDCs was confirmed by immunofluorescent labelling and fluorescence-activated cell sorter analysis. CD137 was also highly expressed by the human cell line HK, which displays many characteristics of in vivo FDCs. The interaction between B cells and FDCs is essential for the GC reactions, and our finding suggests that CD137 plays a role in FDC-regulated B-cell responses.
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