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Mjösberg, Jenny
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Cossarizza, A., Chang, H.-D., Radbruch, A., Andrae, I., Annunziato, F., Bacher, P., . . . Zimmermann, J. (2017). Guidelines for the use of flow cytometry and cell sorting in immunological studies. European Journal of Immunology, 47(10), 1584-1797
Öppna denna publikation i ny flik eller fönster >>Guidelines for the use of flow cytometry and cell sorting in immunological studies
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2017 (Engelska)Ingår i: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 47, nr 10, s. 1584-1797Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

n/a

Ort, förlag, år, upplaga, sidor
Wiley-VCH Verlagsgesellschaft, 2017
Nationell ämneskategori
Klinisk medicin
Identifikatorer
urn:nbn:se:liu:diva-143371 (URN)10.1002/eji.201646632 (DOI)000415363800006 ()29023707 (PubMedID)2-s2.0-85032278767 (Scopus ID)
Anmärkning

Funding Agencies|Fondazione Cariplo (Grant Ricerca Biomedica) [2012/0683]; Italian Ministry of Health (Bando Giovani Ricercatori) [GR-2011-02347324]; European Union Marie Curie Career Integration Grant [322093]; Genome BC; NSERC; German Federal Ministry of Education and Research (BMBF) [01EO1303]; Deutsche Forschungsgemeinschaft (DECIDE, DFG) [WA 1597/4-1, TRR130]; ERC; ISF; French government program: "Investissement davenir: Equipements dExcellence" (EQUIPEX)-FlowCyTech [ANR-10-EQPX-02-01]; Deutsche Forschungsgemeinschaft (DFG) [Me3644/5-1, TRR130/TP24]; National Institutes of Health (R01 grant) [DK056638, HL116340, HL097819]; New York State Department of Health (NYSTEM Program) [N13G262]

Tillgänglig från: 2017-12-05 Skapad: 2017-12-05 Senast uppdaterad: 2017-12-15Bibliografiskt granskad
Pihl, M., Chéramy, M., Mjösberg, J., Ludvigsson, J. & Casas, R. (2011). Increased expression of regulatory T cell-associated markers in recent-onset diabetic children. Open Journal of Immunology, 1(3), 57-64
Öppna denna publikation i ny flik eller fönster >>Increased expression of regulatory T cell-associated markers in recent-onset diabetic children
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2011 (Engelska)Ingår i: Open Journal of Immunology, ISSN 2162-450X, E-ISSN 2162-4526, Vol. 1, nr 3, s. 57-64Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

CD4+CD25hi T cells are thought to be crucial for the maintenance of immunological tolerance to self antigens. In this study, we investigated the frequencies of these cells in the early stage of type 1 diabetes, as well as in a setting of possible pre-diabetic autoimmunity. Hence, the expression of FOXP3, CTLA-4, and CD27 in CD4+ CD25hi T cells was analyzed using flow cytometry in 14 patients with recent onset type 1 diabetes, in 9 at-risk individuals, and 9 healthy individuals with no known risk for type 1 diabetes. Our results show there were no differences in the frequency of CD4+CD25hi cells between groups. However, compared to controls, recent-onset type 1 diabetic patients had higher expression of FOXP3, CTLA-4, and CD27 in CD4+ CD25hi cells from peripheral blood. The median fluorescence intensity of FOXP3 was significantly higher in CD4+CD25hi cells from patients with type 1 diabetes than from controls. Furthermore, a positive correlation between the frequency of FOXP3+ cells and the median fluorescence intensity of FOXP3 was observed among patients with type 1 diabetes. These data suggest that the frequency of CD4+CD25hi FOXP3+ T cells in the periphery is not decreased but rather increased at onset of type 1 diabetes. Thus, functional deficiencies rather than reduced numbers of CD4+CD25hi cells could contribute to the development of type 1 diabetes. 

Ort, förlag, år, upplaga, sidor
Irvine, CA. USA: Scientific Research Publishing, 2011
Nyckelord
Regulatory T cells; Type 1 Diabetes; Autoantibodies
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-75890 (URN)10.4236/oji.2011.13007 (DOI)
Tillgänglig från: 2012-03-15 Skapad: 2012-03-15 Senast uppdaterad: 2017-12-07
Ernerudh, J., Berg, G. & Mjösberg, J. (2011). Regulatory T Helper Cells in Pregnancy and their Roles in Systemic versus Local Immune Tolerance. AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 66, 31-43
Öppna denna publikation i ny flik eller fönster >>Regulatory T Helper Cells in Pregnancy and their Roles in Systemic versus Local Immune Tolerance
2011 (Engelska)Ingår i: AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, ISSN 1046-7408, Vol. 66, s. 31-43Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

Problem During pregnancy, the maternal immune system needs to adapt in order not to reject the semi-allogenic fetus. Method In this review, we describe and discuss the role of regulatory T (Treg) cells in fetal tolerance. Results Treg cells constitute a T helper lineage that is derived from thymus (natural Treg cells) or is induced in the periphery (induced Treg cells). Treg cells are enriched at the fetal-maternal interface, showing a suppressive phenotype. In contrast, Treg cells are not increased in the circulation of pregnant women, and the suppressive capacity is similar to that in nonpregnant women. However, aberrations in Treg frequencies and functions, both systemically and in the uterus, may be involved in the complications of pregnancy. Conclusion Treg cells seem to have distinguished roles locally versus systemically, based on their distribution and phenotype.

Ort, förlag, år, upplaga, sidor
Blackwell Publishing Ltd, 2011
Nyckelord
Cytokines; reproductive immunology; T helper cell; tolerance
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-69811 (URN)10.1111/j.1600-0897.2011.01049.x (DOI)000292337700005 ()
Anmärkning

This is the authors’ version of the publication: Jan Ernerudh, Göran Berg and Jenny Mjösberg, Regulatory T Helper Cells in Pregnancy and their Roles in Systemic versus Local Immune Tolerance, 2011, AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, (66), 31-43. http://dx.doi.org/10.1111/j.1600-0897.2011.01049.x Copyright: John Wiley and Sons http://www.wiley.com/

Tillgänglig från: 2011-08-10 Skapad: 2011-08-08 Senast uppdaterad: 2013-11-07
Ernerudh, J., Forsberg, A., Straka, E., Johansson, E., Bhai Mehta, R., Svensson, J., . . . Jenmalm, M. (2011). T helper cells and T helper cell plasticity in pregnancy in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 131-131. In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY (pp. 131-131). Elsevier, 90(2)
Öppna denna publikation i ny flik eller fönster >>T helper cells and T helper cell plasticity in pregnancy in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 131-131
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2011 (Engelska)Ingår i: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2011, Vol. 90, nr 2, s. 131-131Konferensbidrag, Publicerat paper (Refereegranskat)
Abstract [en]

n/a

Ort, förlag, år, upplaga, sidor
Elsevier, 2011
Nyckelord
Pregnancy, T helper cell, Tolerance
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-70334 (URN)10.1016/j.jri.2011.06.003 (DOI)000293873500002 ()
Tillgänglig från: 2011-09-02 Skapad: 2011-09-02 Senast uppdaterad: 2012-03-25
Edström, M., Mellergård, J., Mjösberg, J., Jenmalm, M., Vrethem, M., Press, R., . . . Ernerudh, J. (2011). Transcriptional characteristics of CD4+ T cells in multiple sclerosis: relative lack of suppressive populations in blood. Multiple Sclerosis, 17(1), 57-66
Öppna denna publikation i ny flik eller fönster >>Transcriptional characteristics of CD4+ T cells in multiple sclerosis: relative lack of suppressive populations in blood
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2011 (Engelska)Ingår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 17, nr 1, s. 57-66Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background:Multiple sclerosis (MS) is hypothetically caused by autoreactive Th1 and Th17 cells, whereas Th2 and regulatory T cells may confer protection. The development of Th subpopulations is dependant on the expression of lineage-specific transcription factors.

Objective:The aim of this study was to assess the balance of CD4+T cell populations in relapsing-remitting MS.

Methods:Blood mRNA expression of TBX21, GATA3, RORC, FOXP3 and EBI3 was assessed in 33 patients with relapsing-remitting MS and 20 healthy controls. In addition, flow cytometry was performed to assess T lymphocyte numbers.

Results:In relapsing-remitting MS, diminished expression of FOXP3 (Treg) was found (p < 0.05), despite normal numbers of CD4+CD25hiTreg. Immunoregulatory EBI3 and Th2-associated GATA3 ([a-z]+) was also decreased in MS (p < 0.005 and p < 0.05, respectively). Expression of TBX21 (Th1) and RORC (Th17) did not differ between patients and controls. Similar changes were observed when analysing beta-interferon treated (n = 12) or untreated (n = 21) patients. Analysis of transcription factor ratios, comparing TBX21/GATA3 and RORC/FOXP3, revealed an increase in the RORC/FOXP3 ratio in patients with relapsing-remitting MS (p < 0.005).

Conclusion:Our findings indicate systemic defects at the mRNA level, involving downregulation of beneficial CD4+phenotypes. This might play a role in disease development by permitting activation of harmful T cell populations.

Ort, förlag, år, upplaga, sidor
Sage Publications, 2011
Nyckelord
EBI3, FOXP3, multiple sclerosis, RORC, T cells, transcription factors
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-64758 (URN)10.1177/1352458510381256 (DOI)000285867200006 ()20847001 (PubMedID)
Tillgänglig från: 2011-02-04 Skapad: 2011-02-04 Senast uppdaterad: 2017-12-11
Mjösberg, J., Berg, G., Jenmalm, M. C. & Ernerudh, J. (2010). FOXP3+ regulatory T cells, T helper 1, T helper 2 and T helper 17 cells in human early pregnancy decidua. Biology of Reproduction, 82(4), 698-705
Öppna denna publikation i ny flik eller fönster >>FOXP3+ regulatory T cells, T helper 1, T helper 2 and T helper 17 cells in human early pregnancy decidua
2010 (Engelska)Ingår i: Biology of Reproduction, ISSN 0006-3363, E-ISSN 1529-7268, Vol. 82, nr 4, s. 698-705Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

In pregnancy, the decidua is infiltrated by leukocytes promoting fetal development without causing immunological rejection. Murine regulatory T (Treg) cells are known to be important immune regulators at this site. The aim of the study was to characterize the phenotype and origin of Treg cells and determine the quantitative relationship between Treg, T-helper type 1 (TH1), TH2, and TH17 cells in first-trimester human decidua. Blood and decidual CD4+ T cells from 18 healthy first-trimester pregnant women were analyzed for expression of Treg-cell markers (CD25, FOXP3, CD127, CTLA4, and human leukocyte antigen-DR [HLA-DR]), chemokine receptors (CCR4, CCR6, and CXCR3), and the proliferation antigen MKI67 by six-color flow cytometry. Treg cells were significantly enriched in decidua and displayed a more homogenous suppressive phenotype with more frequent expression of FOXP3, HLA-DR, and CTLA4 than in blood. More decidual Treg cells expressed MKI67, possibly explaining their enrichment at the fetal-maternal interface. Using chemokine receptor expression profiles of CCR4, CCR6, and CXCR3 as markers for TH1, TH2, and TH17 cells, we showed that TH17 cells were nearly absent in decidua, whereas TH2-cell frequencies were similar in blood and decidua. CCR6+ TH1 cells, reported to secrete high levels of interferon gamma (IFNG), were fewer, whereas the moderately IFNG-secreting CCR6 TH1 cells were more frequent in decidua compared with blood. Our results point toward local expansion of Treg cells and low occurrence of TH17 cells. Furthermore, local, moderate TH1 activity seems to be a part of normal early pregnancy, consistent with a mild inflammatory environment controlled by Treg cells.

Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-53616 (URN)10.1095/biolreprod.109.081208 (DOI)000275814400007 ()20018909 (PubMedID)
Anmärkning

Published online before print December 16, 2009,

Tillgänglig från: 2010-01-26 Skapad: 2010-01-26 Senast uppdaterad: 2017-12-12
Mjösberg, J. (2010). Regulatory T cells in human pregnancy. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Öppna denna publikation i ny flik eller fönster >>Regulatory T cells in human pregnancy
2010 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

During pregnancy, fetal tolerance has to be achieved without compromising the immune integrity of the mother. CD4+CD25highFoxp3+ regulatory cells (Tregs) have received vast attention as key players in immune regulation. However, the identification of human Tregs is complicated by their similarity to activated nonsuppressive T cells. The general aim of this thesis was to determine the antigen specificity, frequency, phenotype and function of Tregs in first to second trimester healthy and severe early-onset preeclamptic human pregnancy. Regarding antigen specificity, we observed that in healthy pregnant women, Tregs suppressed both TH1 and TH2 reactions when stimulated with paternal alloantigens but only TH1, not TH2 reactions when stimulated with unrelated alloantigens. Hence, circulating paternal-specific Tregs seem to be present during pregnancy. Further, by strictly defining typical Tregs (CD4dimCD25high) using flow cytometry, we could show that as a whole, the Treg population was reduced already during first trimester pregnancy as compared with non-pregnant women. This was in contrast to several previous studies and the discrepancy was most likely due to the presence of activated non-suppressive cells in pregnant women, showing similarities to the suppressive Tregs. Although deserving confirmation in a larger sample, severe early-onset preeclampsia did not seem to be associated with alterations in the circulating Treg population. The circulating Treg population was controlled by hormones which, alike pregnancy, reduced the frequency of Foxp3 expressing cells. Yet, in vitro, pregnancy Tregs were highly suppressive of pro-inflammatory cytokine secretion and showed an enhanced capability of secreting immune modulatory cytokines such as IL-4 and IL-10, as well as IL-17, indicating an increased plasticity of pregnancy Tregs. At the fetalmaternal interface during early pregnancy, Tregs, showing an enhanced suppressive and proliferating phenotype, were enriched as compared with blood. Further, CCR6- TH1 cells, with a presumed moderate TH1 activity were enhanced, whereas pro-inflammatory TH17 and CCR6+ TH1 cells were fewer as compared with blood. This thesis adds to and extends the view of Tregs as key players in immune regulation during pregnancy. In decidua, typical Tregs seem to have an important role in immune suppression whereas systemically, Tregs are under hormonal control and are numerically suppressed during pregnancy. Further, circulating pregnancy Tregs show reduced expression of Foxp3 and an increased degree of cytokine secretion and thereby also possibly plasticity. This would ensure systemic defense against infections with simultaneous tolerance at the fetal-maternal interface during pregnancy.

Ort, förlag, år, upplaga, sidor
Linköping: Linköping University Electronic Press, 2010. s. 156
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1163
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-53619 (URN)9789173934602 (ISBN)
Disputation
2010-01-22, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2010-01-26 Skapad: 2010-01-26 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
Mjösberg, J., Jenmalm, M., Berg, G. & Ernerudh, J. (2009). Enrichment of Foxp3(+) T-regs and reduction of T(H)17 cells in human early pregnancy decidua indicate immunosuppressive T cell dominance. In: in JOURNAL OF REPRODUCTIVE IMMUNOLOGY vol 81, issue 2 (pp. 147-147). , 81(2)
Öppna denna publikation i ny flik eller fönster >>Enrichment of Foxp3(+) T-regs and reduction of T(H)17 cells in human early pregnancy decidua indicate immunosuppressive T cell dominance
2009 (Engelska)Ingår i: in JOURNAL OF REPRODUCTIVE IMMUNOLOGY vol 81, issue 2, 2009, Vol. 81, nr 2, s. 147-147Konferensbidrag, Publicerat paper (Refereegranskat)
Abstract [en]

n/a

Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-21508 (URN)10.1016/j.jri.2009.06.199 (DOI)
Tillgänglig från: 2009-10-02 Skapad: 2009-10-02 Senast uppdaterad: 2009-10-02
Mjösberg, J., Svensson, J., Johansson, E., Hellstrom, L., Casas, R., Jenmalm, M., . . . Ernerudh, J. (2009). Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ T-regs in human second trimester pregnancy is induced by progesterone and 17 beta-estradiol. In: Journal of Reproductive Immunology(ISSN 0165-0378), vol 81, issue 2 (pp. 160-161). , 81(2)
Öppna denna publikation i ny flik eller fönster >>Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ T-regs in human second trimester pregnancy is induced by progesterone and 17 beta-estradiol
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2009 (Engelska)Ingår i: Journal of Reproductive Immunology(ISSN 0165-0378), vol 81, issue 2, 2009, Vol. 81, nr 2, s. 160-161Konferensbidrag, Publicerat paper (Refereegranskat)
Abstract [en]

CD4+CD25high regulatory T cells (Tregs) are implicated in maintenance of murine pregnancy. However, reports regarding circulating Treg frequencies in human pregnancy are inconsistent and the functionality and phenotype of these cells in pregnancy have not been clarified. The aim was to determine the frequency, phenotype and function of circulating Tregs in second trimester human pregnancy and the influence of progesterone and 17β-estradiol on Treg phenotype and frequency. Based on expression of Foxp3, CD127 and HLA-DR, as determined by multi-color flow cytometry, we defined a proper CD4dimCD25high Treg population and showed, in contrast to most previous reports, that this population was reduced in second trimester pregnancy. Unexpectedly, Foxp3 expression was decreased in the Treg, as well as in the CD4+ population. These changes could be replicated in an in vitro system resembling the pregnancy hormonal milieu, where 17β-estradiol, and in particular progesterone, induced, in line with the pregnancy situation, a reduction of CD4dimCD25highFoxp3+ cells in PBMC from non-pregnant women. By co-culturing FACS-sorted Tregs and autologous CD4+CD25- responder cells, we showed that Tregs from pregnant women still displayed the same suppressive capacity as non-pregnant women in terms of suppressing IL-2, TNF-α and IFN-γ secretion from responder cells while efficiently producing IL-4 and IL-10. Our findings support the view of hormones, particularly progesterone, as critical regulators of Tregs in pregnancy. Further, we suggest that in the light of the results of this study, early data on circulating Treg frequencies in pregnancy need re-evaluation.

Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-21510 (URN)10.1016/j.jri.2009.06.225 (DOI)
Anmärkning
Original Publication: Jenny Mjösberg, J Svensson, E Johansson, L Hellstrom, Rosaura Casas, Maria Jenmalm, R Boij, L Matthiesen, Jan-Ingvar Jönsson, Göran Berg and Jan Ernerudh, Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ Tregs in human second trimester pregnancy is induced by progesterone and 17 beta-estradiol, 2009, JOURNAL OF REPRODUCTIVE IMMUNOLOGY, (81), 2, 160-161. http://dx.doi.org/10.1016/j.jri.2009.06.225 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/ Tillgänglig från: 2009-10-02 Skapad: 2009-10-02 Senast uppdaterad: 2010-05-19
Mjösberg, J., Svensson, J., Johansson, E., Hellström, L., Casas, R., Jenmalm, M., . . . Ernerudh, J. (2009). Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ Tregs in human second trimester pregnancy is induced by progesterone and 17θ-estradiol. Journal of Immunology, 183(1), 759-769
Öppna denna publikation i ny flik eller fönster >>Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ Tregs in human second trimester pregnancy is induced by progesterone and 17θ-estradiol
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2009 (Engelska)Ingår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 183, nr 1, s. 759-769Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

CD4+CD25high regulatory T cells (Tregs) are implicated in the maintenance of murine pregnancy. However, reports regarding circulating Treg frequencies in human pregnancy are inconsistent, and the functionality and phenotype of these cells in pregnancy have not been clarified. The aim of this study was to determine the frequency, phenotype, and function of circulating Tregs in the second trimester of human pregnancy and the influence of progesterone and 17β-estradiol on Treg phenotype and frequency. Based on expressions of Foxp3, CD127, and HLA-DR as determined by multicolor flow cytometry, we defined a proper CD4dimCD25high Treg population and showed, in contrast to most previous reports, that this population was reduced in second trimester of pregnancy. Unexpectedly, Foxp3 expression was decreased in the Treg, as well as in the CD4+ population. These changes could be replicated in an in vitro system resembling the pregnancy hormonal milieu, where 17β-estradiol, and in particular progesterone, induced, in line with the pregnancy situation, a reduction of CD4dimCD25highFoxp3+ cells in PBMC from nonpregnant women. By coculturing FACS-sorted Tregs and autologous CD4+CD25 responder cells, we showed that Tregs from pregnant women still displayed the same suppressive capacity as nonpregnant women in terms of suppressing IL-2, TNF-, and IFN- secretion from responder cells while efficiently producing IL-4 and IL-10. Our findings support the view of hormones, particularly progesterone, as critical regulators of Tregs in pregnancy. Furthermore, we suggest that in the light of the results of this study, early data on circulating Treg frequencies in pregnancy need reevaluation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-53104 (URN)10.4049/jimmunol.0803654 (DOI)000275119400082 ()19535629 (PubMedID)
Tillgänglig från: 2010-01-26 Skapad: 2010-01-15 Senast uppdaterad: 2017-12-12Bibliografiskt granskad
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