| 1. |
- Copland, DA, et al.
(författare)
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Monoclonal antibody-mediated CD200 receptor signaling suppresses macrophage activation and tissue damage in experimental autoimmune uveoretinitis
- 2007
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 171:2, s. 580-588
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Tidskriftsartikel (refereegranskat)abstract
- Macrophage responses are regulated by multiple secreted factors as well as by cell surface receptors, including the inhibitory signals resulting from ligation of myeloid CD200 receptors (CD200R) by the widely distributed CD200. In the absence of CD200, animals display increased susceptibility to autoimmunity and earlier onset aggressive autoimmune disease. In these current experiments, an agonist monoclonal rat anti-mouse CD200R (DX109) antibody delivered a negative signal to bone marrow-derived macrophages, which suppressed interferon (IFN)-mediated nitric oxide (NO) and interleukin-6 production. Experimental autoimmune uveoretinitis (EAU) was used as a model of organ-specific autoimmunity in the eye, a tissue with extensive neuronal and endothelial CD200 expression. In mice lacking CD200 (CD200-/-), increased numbers of retina-infiltrating macrophages displaying heightened NO responses were observed during EAU. In addition, we aimed to suppress disease by maintaining tonic suppression of macrophage activation via CD200R. Systemically administered DX109 monoclonal antibody suppressed EAU despite maintained T-cell proliferation and IFN production. Furthermore, locally administered DX109 monoclonal antibody resulted in an earlier resolution of disease. These experiments demonstrate that promoting CD200R-mediated signaling can successfully prevent full expression of IFN-mediated macrophage activation and protect against tissue damage during autoimmune responses.
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| 2. |
- Fagerås Böttcher, Malin, 1969-, et al.
(författare)
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Cytokine responses to allergens during the first 2 years of life in Estonian and Swedish children
- 2006
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 36:5, s. 619-628
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Tidskriftsartikel (refereegranskat)abstract
- Background The prevalence of atopic disease among children in the formerly socialist countries in Europe, with a life style similar to that prevailing in Western Europe 30–40 years ago, is low, whereas there has been a pronounced increase in industrialized countries over the last decades. The environment during infancy influences the risk of developing allergy for many years, perhaps even for life.Objective To investigate the development of allergen-specific cytokine responses during the first 2 years of life in two geographically adjacent countries with marked differences in living conditions and incidence of atopic diseases, i.e. Estonia and Sweden.Methods The development of immune responses to food (β-lactoglobulin (BLG) and ovalbumin (OVA)) and inhalant (cat and birch) allergens was studied from birth up to the age of 2 years in 30 Estonian and 76 Swedish infants. Clinical investigation and skin prick tests were performed and blood samples were obtained at birth and at 3, 6, 12 and 24 months.Results The levels of IL-5, IL-10 and IL-13 secreted by peripheral blood mononuclear cells stimulated with BLG, OVA and cat allergen in Estonian and Swedish infants declined during the first 3 months of life. All cytokines then progressively increased in the Swedish infants, indicating the replacement of non-specifically responding immature cord blood T cells with specific T memory cells, which are primed postnatally. The resurgence of allergen-specific responses in the Estonian infants was less marked. These differences were particularly notable for birch-specific T cell responses, which correlated with development of atopic disease in the Swedish children.Conclusions The development of specific T cell memory to food and inhalant allergens during the first 2 years of life differs between infants living in Sweden and Estonia, and mirrors the disparate patterns of expression of allergic disease which subsequently develops in the respective populations.
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| 3. |
- Jenmalm, Maria, 1971-, et al.
(författare)
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Regulation of myeloid cell function through the CD200 receptor
- 2006
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Ingår i: Journal of Immunology. - 0022-1767 .- 1550-6606. ; 176:1, s. 191-199
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Tidskriftsartikel (refereegranskat)abstract
- Myeloid cells play pivotal roles in chronic inflammatory diseases through their broad proinflammatory, destructive, and remodeling capacities. CD200 is widely expressed on a variety of cell types, while the recently identified CD200R is expressed on myeloid cells and T cells. CD200 deletion in vivo results in myeloid cell dysregulation and enhanced susceptibility to autoimmune inflammation, suggesting that the CD200-CD200R interaction is involved in immune suppression. We demonstrate in this study that CD200R agonists suppress mouse and human myeloid cell function in vitro, and also define a dose relationship between receptor expression and cellular inhibition. IFN-γ- and IL-17-stimulated cytokine secretion from mouse peritoneal macrophages was inhibited by CD200R engagement. Inhibitory effects were not universal, as LPS-stimulated responses were unaffected. Inhibition of U937 cell cytokine production correlated with CD200R expression levels, and inhibition was only observed in low CD200R expressing cells, if the CD200R agonists were further cross-linked. Tetanus toxoid-induced human PBMC IL-5 and IL-13 secretion was inhibited by CD200R agonists. This inhibition was dependent upon cross-linking the CD200R on monocytes, but not on cross-linking the CD200R on CD4+ T cells. In all, we provide direct evidence that the CD200-CD200R interaction controls monocyte/macrophage function in both murine and human systems, further supporting the potential clinical application of CD200R agonists for the treatment of chronic inflammatory diseases. Copyright © 2005 by The American Association of Immunologists, Inc.
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| 4. |
- Voor, Tina, et al.
(författare)
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Atopic sensitization and atopic dermatitis in Estonian and Swedish infants
- 2005
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 35:2, s. 153-159
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early life events seem to have a major impact on the development of tolerance or sensitization. Objective: The aim of the study was to compare the prevalence of sensitization and atopic dermatitis (AD) during the first 2 years of life in Estonia and in Sweden. Methods: Two groups comprising 110 Estonian and 123 Swedish infants were followed from birth up to 2 years of age. Data about symptoms of allergy, infections and use of antibiotics were obtained by questionnaires. Clinical examinations, skin prick tests (SPTs) with food and inhalant allergens, and blood sampling for IgE analyses were carried out at 3, 6, 12 and 24 months. Results: The cumulative incidence of AD and positive SPTs were lower in the Estonian than the Swedish infants (14% vs. 24%, P = 0.06 and 13% vs. 24%, P = 0.03), while circulating IgE antibodies were more common (39% vs. 27%, P = 0.06) and often present without any clinical significance in Estonian children. Estonian infants had respiratory illnesses more often and they had received antibiotics more frequently. Use of antibiotics increased the risk for positive SPT in the Estonian (odds ratio = 1.7, 95% confidence interval = 1.1 - 2.5), but not in the Swedish infants. This may be explained by the use of broad-spectrum antibiotics in Estonia, while in Sweden mostly penicillin was prescribed. Conclusions: The prevalence of AD and positive SPTs was lower in the Estonian than the Swedish infants, while circulating IgE antibodies were more common and often present without any clinical significance. These differences cannot simply be explained by infections, or use of broad-spectrum antibiotics in the two countries, although more the natural lifestyle in Estonia may be contributing factor. © 2005 Blackwell Publishing Ltd.
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