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  • 1
    Electronic Resource
    Electronic Resource
    Reversal of T-Cell Anergy in Autoimmune (NZB X NZW)F1 Mice by Transfer with Non-Antigen Specific CD4+ T Cells from Young, Syngeneic Donors (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 34 (1991), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The F1 hybrid of NZB and NZW mice is a well-known model of ds systemic lupus erythematosus characterized by B-cell hyperactivity, production of autoantibodies and immune-complex formation. These phenomena have been regarded as pathogenetic for the development of glomerulonephritis and early death in renal failure. U has been previously reported that aged and overt diseased NZB/W mice also display impaired T-cell responses. In the present report we demonstrate an age-dependent decline in the capacity of NZB/W mice to mount in vivo cutaneous delayed type hypersensitivity (DTH) and antibody responses to a hapten. oxazolone (OXA). Moreover, in vitro proliferative response lo Concanavalin A (Con A) and production of interleukin 2 (lL-2) were severely depressed in aged NZB/W mice, In transfer experiments we show that a single i. p. injection of non-immune mononuclear spleen cells from young NZB/W mice to old diseased syngeneic recipients restores DTH reactivity and increases the antibody response to OXA, This effect is a CD4+- dependent process since the restoration of T-cell responses was abrogated upon elimination of CD4+ donor T cells. Overall, our results indicate that limited numbers ofCD4* T cells display substantial immunoregulatory properties reversing the state of anergy in autoimmune NZB/W mice.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1991.tb01600.x
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  • 2
    Electronic Resource
    Electronic Resource
    Expression of Heterozygous lpr Gene in MRL Mice (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 32 (1990), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Recently we showed that not only homozygous MRL lpr/lpr mice but also heterozygous MRL +/lpr mice display defective antigen- and mitogen-driven T-cell responses as well as polyclonal B-cell activation compared with congeneic MRL +/+ mice. In this study we examined die impact of the heterozygous lpr gene on organ pathology in kidneys, joints, and salivary glands, as well as serum levels of immunoglobulins and autoantibodies in young and old MRL mice. Only 1 out of 17 heterozygous lpr-bearing MRL mice developed clinically overt renal disease with significant proteinuria and haematuria during the first year of life. However, examination of Ig and C3 deposits in glomeruli of kidneys from these mice revealed that the expression of the heterozygous lpr gene in MRL mice accelerates glomerulonephritis in addition, histological examination of the submandibular salivary glands showed an increased focus score in heterozygous MRL mice at 4–5 months of age compared with that of matched congeneic +/+ mice. In contrast, no signs of arthropathy were registered in the heterozygous lpr-bearing MRL mice. Heterozygous MRL mice displayed an expanding lymphoid system as evaluated by significantly increased spleen and lymph node weights com pared with those of matched MRL +/+ mice. Further evidence for immunomodulatory properties of the heterozygous lpr gene was obtained when analysing serum levels of IgG, IgM, and autoantibodies. Thus, heterozygous MRL +/lpr mice produced significantly higher levels of both Ig and autoantibodies than matched MRL +/+ mice. We conclude that the expression of the heterozygous lpr gene in MRL mice results in acceleration of the autoimmune process, giving rise to precocious clinical disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1990.tb02887.x
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  • 3
    Electronic Resource
    Electronic Resource
    Expression of Heterozygous lpr Gene in MRL Mice (1989)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 30 (1989), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The presence of the homozygous lpr gene (lpr/lpr) in MRL mice has been regarded as mandatory for the development of the early onset of lupus disease, T-cell dysfunctions, and polyclonal B-cell activation. Congeneic MRL mice lacking the lpr gene (MRL +/+) display neither the lupus disease nor the immunological abnormalities within the first year of life. In this study we examined the cellular functions of MRL mice heterozygous at the lpr locus. The results indicate that MRL mice heterozygous at the lpr locus display intermediate delayed-type hypersensitivity compared with homozygous lpr/lpr mice on the one hand and congeneic +/+ mice on the other. Furthermore, proliferative responses to concanavalin A, measured by uptake of [3H]thymidine, were significantly lower in MRL mice heterozygous at the lpr locus than in +/+ mice, but significantly higher than in homozygous MRL lpr/lpr mice. Polyclonal B-cell activation, assessed by measurement of frequencies of IgG-secreting spleen cells, a prominent feature in MRL lpr/lpr mice, was significantly lower in lpr/+ mice and totally absent in +/+ mice. Furthermore, spleen cells spontaneously secreting auto-antibodies were found in large numbers in MRL lpr/lpr mice and in considerably lower but still significant numbers in heterozygous MRL+/lpr mice. In contrast, spleen cells from matched MRL +/+ mice did not display any spontaneous autoantibody production. Taken together, these data provide evidence for immunomodulatory properties of the heterozygous lpr gene.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1989.tb02450.x
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  • 4
    Electronic Resource
    Electronic Resource
    Generation of Monoclonal Rheumatoid Factors after Immunization with Collagen II-Anti-Collagen II Immune Complexes (1986)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 24 (1986), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Two monoclonal IgG rheumatoid factors were obtained alter hybridization of spleen cells from DBA/1 mice immunized with immune complexes containing native collagen type II and a monoclonal anti-collagen II antibody. One of these rheumatoid factors reacted not only with purified murine Fc fragments, but also with Fab fragments of the anti-collagen II antibody used for immunization, whereas no reactivity was seen with Fab fragments from normal mouse IgG. The findings demonstrate the ability of immune complexes encompassing native collagen type II to induce production of IgG rheumatoid factors, and suggest that an idiotypic relationship may exist between certain rheumatoid factors and anti-collagen II antibodies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1986.tb02086.x
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  • 5
    Electronic Resource
    Electronic Resource
    Detection of Single Antibody-Secreting Cells Generated After in Vitro Antigen-Induced Stimulation of Human Peripheral Blood Lymphocytes (1984)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 19 (1984), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Culture and assay procedures are described for the generation and the subsequent detection of single antigen-specific antibody-secreting cells after in vitro stimulation of human peripheral blood lymphocytes with tetanus toxoid. Simple, specific and sensitive, this new assay-culture system is well suited for the analysis of specific antibody production in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1984.tb00968.x
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  • 6
    Electronic Resource
    Electronic Resource
    Role of T Lymphocytes in Experimental Staphylococcus aureus Arthritis (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 39 (1994), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Using a recently developed murine model of haematogenously induced Staphylococcus aureus, the authors have characterized the phenotypes and functional properties of inflammatory cells present in the synovium of arthritic mice. The results show that large numbers of granulocytes and macrophages were observed in the inflamed synovia within 24 h of inoculation of S. aureus strain LS-1. Many of the synovial macrophage-like cells stained for cytoplasmic IL-1α and TN F-α. Subsequently (〈 48 h later), a prominent infiltration of T lymphocytes, predominantly of CD4+ phenotype, was observed. Some of the T lymphocytes stained for IL-2 receptor and intracytoplasmicinterferon-γ (IFN-γ). Surprisingly, in spite of the severe inflammatory process, very few cells expressed MHC class-II molecules in the arthritic synovia. In addition, in vivo depletion of CD4 + T-cells resulted in a considerably milder course of staphylococcal arthritis. The similarities in the phenotype expression of synovial cells and central role of T-cells in S. aureus arthritis as well as in non-infectious models of arthritis, indicate that the process governing joint destruction is likely to be the same, irrespective of the initial stimulus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1994.tb03392.x
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  • 7
    Electronic Resource
    Electronic Resource
    Histocompatibility Complex Gene Products and Exposure to Oestrogen: Two Independent Disease Accelerating Factors in Murine Lupus (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 38 (1993), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A number of studies have demonstrated that oestrogen exerts a significant impact on the course of experimental autoimmune diseases. Exposure to oestrogen aggravates SLE glomerulonephritis whereas the opposite outcome has been demonstrated in experimental arthritis, vasculitis, thyroiditis, and sialadenitis. In this report we have analysed the respective impact of H-2z linked gene products and long-term treatment with physiological doses of oestradiol on clinical and immunological variables in castrated backcrosses of lupus prone NZB/W and NZB mice.Our results demonstrate that H-2z linked gene products accelerate B-cell activation and stimulate autoantibody production resulting in aggravation of glomerulonephritis and precocious death in renal failure. These H-2z linked gene products do not influence T-cell mediated sialadenitis. Irrespectively of the H-2 haplotype of the mice, administration of oestrogen resulted in intense polyclonal B cell activation and aggravation of glomerulonephritis. However, exposure to oestrogen resulted in amelioration of sialadenitis. Notably, our result indicates that B-cell activation achieved by oestrogen and H-2z gene linked products, respectively is mediated by independent mechanisms.In addition, we have developed a predictive in vivo test that permits forecasts regarding efficiency of oestrogen treatment for suppression of T-cell mediated lesions. Using this test procedure in young, clinically healthy SLE mice we have been able to prove that animals displaying suppressed delayed type hypersensitivity (DTH) after short-term oestrogen exposure showed significantly lower long-term morbidity regarding development of sialadenitis upon continuous treatment with physiological doses of oestradiol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1993.tb01736.x
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  • 8
    Electronic Resource
    Electronic Resource
    Participation of Vβ4+-, Vβ7+-, and Vβ11+-T Lymphocytes in Haematogenously Acquired Staphylococcus aureus Nephritis (1996)
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 44 (1996), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The most frequent pathogen in haematogenously acquired kidney infections in humans is Staphylococcus aureus. In order to characterize in situ the immunological patterns of septic nephritis we developed a murine model of this disease. A single intravenous injection of S. aureus producing toxic shock syndrome toxin-1 resulted in high frequency of inflammatory kidney lesions. Histopathologically, both focal and diffuse inflammatory infiltrates were seen in kidney cortex and medulla. Immunohistochemical evaluation revealed high numbers of Mac-1+ phagocytic cells as well as CD4+- and CD8+-lymphocytes. The expansion of lymphocytes carrying T-cell receptor Vβ chain 4, 7, and 11 families in the kidney was observed. Our results suggest that the haematogenously acquired kidney infection by superantigen-producing staphylococci leads to migration, in situ activation and expansion of responding T-lymphocyte subsets.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.1996.d01-309.x
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  • 9
    Electronic Resource
    Electronic Resource
    Limited T-Cell Receptor V Gene Usage in Inclusion Body Myositis (1996)
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 43 (1996), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Inclusion body myositis (IBM) is a chronic, progressive inflammatory myopathy. The inflammatory infiltrates are dominated by T cells, which frequently invade muscle fibres. The present study was performed to characterize the usage of the variable (V)segment of the T-cell receptor of muscle infiltrating cells in IBM. Using the reverse transcriptase polymerase chain reaction (RT-PCR) technique the authors analysed the expression of 22 Vα and 24 Vβ families in muscle tissue from six patientswith IBM displaying intense inflammatory cell infiltration. The following Vα/Vβ families appeared in at least 50% of the patients: Vα1, 5, 7, 15, 16, 17, 20, 21, 22 and Vβ3, 5.2, 8, 12, 14, 22. In all patients Vα7, 16 and Vβ8 wereexpressed in muscle tissue. Furthermore, in two of the patients peripheral blood lymphocytes (PBL) were investigated in parallel. There was a restricted usage of Vα and Vβ families in muscle in comparison to PBL, indicating a selective homing orlocal proliferation of T lymphocytes in the inflammatory lesions in IBM.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.1996.d01-10.x
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  • 10
    Electronic Resource
    Electronic Resource
    Local T-Cell Proliferation and Differentiation in Inflammatory Myopathies (1995)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 41 (1995), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Our objective was to investigate the patterns of proliferation and differentiation of infiltrating cells in inflammatory myopathies. Immunohistochemical staining was performed on muscle biopsy specimens from 18 patients with inclusion body myositis, polymyositis and dermatomyositis using monoclonal and polyclonal antibodies.An abundance of cells were TNF-α+ (4–8%), ICAM-1+ (7–65%). IFN-γ+ (3–6%), and Ki-67+ (4–8%). It was shown that 70% of the Ki-67+ cells were Ki-67+CD3+ cells. Very few mononuclear cells were IL-2R+. MHC-I expression was found on nearly all muscle fibres in all cases, while MHC-II expression was found on occasional muscle fibres in 1/3 of cases. Analysis of repeated biopsies from four IBM patients after prednisolone treatment showed no change in the proportions of TNF-α, ICAM-1, IFN-γ or Ki-67 positive cells. In inflammatory myopathies there is an intense proliferation and differentiation of inflammatory cells in situ, indicating a local stimulation of the inflammatory process.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1995.tb03587.x
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