| 1. |
- Grindebacke, Hanna, 1977, et al.
(författare)
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Defective suppression of Th2 cytokines by CD4CD25 regulatory T cells in birch allergics during birch pollen season
- 2004
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Ingår i: Clin Exp Allergy. ; 34:9, s. 1364-72
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: CD4(+)CD25+ regulatory T cells suppress proliferation and cytokine production by human T cells both to self-antigens and exogenous antigens. Absence of these cells in human newborns leads to multiple autoimmune and inflammatory disorders together with elevated IgE levels. However, their role in human allergic disease is still unclear. OBJECTIVE: This study aimed to evaluate the capacity of CD4(+)CD25+ regulatory T cells to suppress proliferation and cytokine production outside and during birch-pollen season in birch-allergic patients relative to non-allergic controls. METHODS: CD4+ cells were obtained from blood of 13 birch-allergic patients and six non-allergic controls outside pollen season and from 10 birch-allergic patients and 10 non-allergic controls during birch-pollen season. CD25+ and CD25- fractions were purified with magnetic beads and cell fractions, alone or together in various ratios, were cultured with antigen-presenting cells and birch-pollen extract or anti-CD3 antibody. Proliferation and levels of IFN-gamma, IL-13, IL-5 and IL-10 were measured by thymidin incorporation and ELISA, respectively. Numbers of CD25+ cells were analysed by flow cytometry. RESULTS: CD4(+)CD25+ regulatory T cells from both allergics and non-allergics potently suppressed T cell proliferation to birch allergen both outside and during birch-pollen season. However, during season CD4(+)CD25+ regulatory T cells from allergic patients but not from non-allergic controls were defective in down-regulating birch pollen induced IL-13 and IL-5 production, while their capacity to suppress IFN-gamma production was retained. In contrast, outside pollen season the regulatory cells of both allergics and non-allergic controls were able to inhibit T-helper 2 cytokine production. CONCLUSION: This is the first study to show differential suppression of Th1 and Th2 cytokines, with CD4(+)CD25+ regulatory T cells from birch-pollen-allergic patients being unable to down-regulate Th2, but not Th1 responses during birch-pollen season.
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| 2. |
- Grindebacke, Hanna, 1977, et al.
(författare)
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Specific Immunotherapy to Birch Allergen Does not Enhance Suppression of Th2 Cells by CD4(+)CD25 (+) Regulatory T Cells During Pollen Season.
- 2009
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Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 1573-2592 .- 0271-9142. ; 29:6, s. 752-60
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of this study was to investigate the suppressive capacity of CD25(+) regulatory T cells on birch allergen-induced T-cell responses during the first birch pollen season after initiation of specific immunotherapy (SIT). METHODS: CD25(pos) and CD25(neg) T cells were purified from blood of birch-allergic SIT patients and birch-allergic controls, stimulated with birch pollen extract, and analyzed for T-cell proliferation and production of interferon gamma (IFN-gamma), interleukin (IL)-5 and IL-10. RESULTS: We show that allergen-induced proliferation and IFN-gamma production were suppressed equally well by CD25(pos) T cells from SIT patients and controls, while the IL-5 production was not suppressed by either of the groups. IL-10 levels were higher in SIT patients relative to controls only when CD25(neg) and CD25(pos) were cultured together. Furthermore, neither FOXP3 levels nor proportions of CD25(high) T cells were enhanced in SIT patients compared to allergic controls. DISCUSSION: These results suggest that the Th2-suppressive capacity of allergen-stimulated CD25(pos) Treg in vitro is not improved by SIT in spite of increased IL-10 production from T cells.
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| 3. |
- Tengvall, Sara, 1977, et al.
(författare)
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Gene Therapy Induces Antigen-Specific Tolerance in Experimental Collagen-Induced Arthritis
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Here, we investigate induction of immunological tolerance by lentiviral based gene therapy in a mouse model of rheumatoid arthritis, collagen II-induced arthritis (CIA). Targeting the expression of the collagen type II (CII) to antigen presenting cells (APCs) induced antigen-specific tolerance, where only 5% of the mice developed arthritis as compared with 95% of the control mice. In the CII-tolerized mice, the proportion of Tregs as well as mRNA expression of SOCS1 (suppressors of cytokine signaling 1) increased at day 3 after CII immunization. Transfer of B cells or non-B cell APC, as well as T cells, from tolerized to naive mice all mediated a certain degree of tolerance. Thus, sustainable tolerance is established very early during the course of arthritis and is mediated by both B and non-B cells as APCs. This novel approach for inducing tolerance to disease specific antigens can be used for studying tolerance mechanisms, not only in CIA but also in other autoimmune diseases.
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| 4. |
- Wing, Kajsa, 1977, et al.
(författare)
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CD4 T cell activation by myelin oligodendrocyte glycoprotein is suppressed by adult but not cord blood CD25+ T cells.
- 2003
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Ingår i: European journal of immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 33:3, s. 579-87
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory T cells expressing CD25 have been shown to protect rodents from organ-specific autoimmune diseases. Similar CD25+ cells with a memory phenotype exerting suppressive function after polyclonal or allogeneic stimulation are also present in adult human blood. We demonstrate that adult human CD25+ cells regulate the response to myelin oligodendrocyte glycoprotein (MOG), as depletion of CD25(+) cells increases responses of PBMC and the addition of purified CD25+ cells suppresses MOG-specific proliferation and IFN-gamma production of CD4(+)CD25(-) T cells. In contrast, cord blood CD25+ cells do not inhibit responses to self antigens, and only a small subpopulation of cord CD25+ cells expresses the typical phenotype of adult regulatory T cells (CD45RA(-) and GITR(+)) enabling suppression of polyclonal responses. We conclude that activation of self-reactive T cells in normal healthy individuals is prevented by the presence of self-antigen-specific CD25+ regulatory T cells and that the majority of these cells mature after birth.
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| 5. |
- Wing, Kajsa, 1977, et al.
(författare)
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CD4+ CD25+ FOXP3+ regulatory T cells from human thymus and cord blood suppress antigen-specific T cell responses
- 2005
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Ingår i: Immunology. ; 115:4, s. 516-25
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Tidskriftsartikel (refereegranskat)abstract
- Activation of self-reactive T cells in healthy adults is prevented by the presence of autoantigen-specific CD4+CD25+ regulatory T cells (CD25+ Treg). To explore the functional development of autoantigen-reactive CD25+ Treg in humans we investigated if thymic CD25+ Treg from children aged 2 months to 11 years and cord blood CD25+ Treg are able to suppress proliferation and cytokine production induced by specific antigens. While CD4+CD25- thymocytes proliferated in response to myelin oligodendrocyte glycoprotein (MOG), tetanus toxoid and beta-lactoglobulin, suppression of proliferation was not detected after the addition of thymic CD25+ Treg. However, CD25+ Treg inhibited interferon (IFN)-gamma production induced by MOG, which indicates that MOG-reactive CD25+ Treg are present in the thymus. In contrast, cord blood CD25+ Treg suppressed both proliferation and cytokine production induced by MOG. Both cord blood and thymic CD25+ Treg expressed FOXP3 mRNA. However, FOXP3 expression was lower in cord blood than in thymic CD25+ T cells. Further characterization of cord blood CD25+ T cells revealed that FOXP3 was highly expressed by CD25+CD45RA+ cells while CD25+CD45RA- cells contained twofold less FOXP3, which may explain the lower expression level of FOXP3 in cord blood CD25+ T cells compared to thymic CD25+ T cells. In conclusion, our data demonstrate that low numbers of MOG-reactive functional CD25+ Treg are present in normal thymus, but that the suppressive ability of the cells is broader in cord blood. This suggests that the CD25+ Treg may be further matured in the periphery after being exported from the thymus.
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| 6. |
- Wing, Kajsa, 1977, et al.
(författare)
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CD4+CD25+-regulatory T cells from mouse to man
- 2005
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Ingår i: Scand J Immunol. ; 62:1, s. 1-15
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Forskningsöversikt (refereegranskat)abstract
- Immunological tolerance is one of the fundamental concepts of the immune system. During the past decade, CD4+CD25+-regulatory T cells have emerged as key players in the development of tolerance to autoantigens as well as to foreign antigens. Still many questions remain illusive regarding the basic properties of CD4+CD25+-regulatory T cells. This review aims to recapitulate some of the current understandings about the phenotype, function and clinical relevance of murine and human CD4+CD25+-regulatory T cells.
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| 7. |
- Wing, Kajsa, 1977
(författare)
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Inhibition of T cell responses to autoantigens and allergens by CD25+ regulatory T cells from thymus, cord and adult blood
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Autoimmune diseases and allergies are a growing problem in the western world today. Tolerance is primarily established by clonal deletion in the thymus. Despite this auto-reactive T cells are normally present in most individuals, which suggests that mechanisms of peripheral tolerance operate to silence potentially pathogenic T cells. Current evidence points to CD4+CD25+ regulatory T cells (CD25+ Treg) as an active mechanism to suppress auto-reactive T cells that escape central tolerance. The aim of this thesis was to investigate if CD25+ Treg, similar to the murine counterpart, could be found and characterized in human lymphoid tissues. To this end, mononuclear cells were isolated from adult peripheral blood, cord blood and thymus and studied by flow cytometry and in functional studies of proliferation and cytokine production. We demonstrate that CD4+CD25+ T cells expressing intracellular CD152 (CTLA-4) and elevated levels of CD122, both hallmarks of murine CD25+Treg, are present in thymus as well as in cord and adult blood. We further show that CD25+ Treg in adults potently suppress T cell proliferation and IFN-gamma production in response to the auto-antigen myelin oligodendrocyte glycoprotein (MOG). By increasing the sensitivity in the suppression assay we found that also cord blood CD25+ Treg suppress MOG-induced proliferation and cytokine production. Interestingly, thymic CD25+ Treg did not inhibit the proliferation but did suppress IFN-gamma, which demonstrates the presence of MOG-specific CD25+ Treg in the thymus. In addition to the above-mentioned studies on healthy subjects, we investigated if patients suffering from birch allergy showed signs of defective CD25+ Treg when compared to healthy individuals. We found that birch allergic patients were unable to suppress Th2 cytokines during birch pollen season, while no differences were detected outside season when compared to healthy controls. In summary, our results demonstrate that CD25+ Treg are educated in the thymus but expand and improve their suppressive ability in the periphery mainly after birth.
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