| 1. |
- Aldridge, Jonathan, et al.
(författare)
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Blood PD-1+TFh and CTLA-4+CD4+ T cells predict remission after CTLA-4Ig treatment in early rheumatoid arthritis.
- 2022
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:3
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with CTLA-4Ig blocks T cell activation and is clinically effective in rheumatoid arthritis (RA). However, it is unknown if specific CD4+ T cell subsets in blood at baseline predict remission after CTLA-4Ig, or other biological treatments with different modes of action, and how treatment affects CD4+ T cells in patients with untreated early RA (eRA).This study included 60 patients with untreated eRA from a larger randomised trial. They were treated with methotrexate combined with CTLA-4Ig (abatacept, n = 17), anti-IL6 receptor (tocilizumab, n = 21) or anti-TNF (certolizumab-pegol, n = 22). Disease activity was assessed by clinical disease activity index (CDAI), DAS28, swollen joint counts, tender joint counts, CRP and ESR. The primary outcome was CDAI remission (CDAI ≤ 2.8) at week 24. Proportions of 12 CD4+ T cell subsets were measured by flow cytometry at baseline and after 4, 12 and 24 weeks of treatment.In patients treated with CTLA-4Ig, the proportions of PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline predicted CDAI remission at week 24. CD4+ T cell subset proportions could not predict remission after treatment with anti-IL6R or anti-TNF. The percentage of regulatory T cells (Tregs) expressing CTLA-4 decreased in all treatment arms by 24 weeks, but only CTLA-4Ig treatment significantly reduced the proportions of Tregs and PD-1+T follicular helper (TFh) cells.These findings indicate that circulating proportions PD-1+TFh and CTLA-4+ conventional CD4+ T cells at baseline may serve as predictive biomarkers for remission in early RA after CTLA-4Ig treatment.
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| 2. |
- Aldridge, Jonathan, et al.
(författare)
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T helper cells in synovial fluid of patients with rheumatoid arthritis primarily have a Th1 and a CXCR3(+)Th2 phenotype
- 2020
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The majority of CD4(+)T helper (Th) cells found in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) express CXCR3, a receptor associated with Th1 cells. In blood, subsets of Th2 and Th17 cells also express CXCR3, but it is unknown if these cells are present in RA SF or how cytokines from these subsets affect cytokine/chemokine secretion by fibroblast-like synoviocytes (FLS) from patients with RA. Methods We examined the proportions of Th1, Th2, CXCR3(+)Th2, Th17, CXCR3(+)Th17, Th1Th17, peripheral T helper (TPh) and T follicular helper (TFh) cells in paired SF and blood, as well as the phenotype of TPh and TFh cells in RA SF (n = 8), by the use of flow cytometry. We also examined the cytokine/chemokine profile in paired SF and plasma (n = 8) and in culture supernatants of FLS from patients with chronic RA (n = 7) stimulated with Th-associated cytokines, by the use of cytometric bead arrays and ELISA. Cytokine receptor expression in FLS (n = 3) were assessed by the use of RNA sequencing and qPCR. Results The proportions of Th1 and CXCR3(+)Th2 cells were higher in SF than in blood (P < 0.05). TPh and PD-1(high)TFh in RA SF were primarily of a Th1 and a CXCR3(+)Th2 phenotype. Moreover, the levels of CXCL9, CXCL10, CCL20, CCL2, CXCL8, IL-6 and IL-10 were higher in SF than in plasma (P < 0.05). Lastly, IL-4, IL-13 and IL-17A induced RA FLS to secrete proinflammatory IL-6, CCL2, CXCL1 and CXCL8, while IFN gamma mainly induced CXCL10. Conclusion These findings indicate that not only Th1 but also CXCR3(+)Th2 cells may have a pathogenic role in RA synovial inflammation.
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| 3. |
- Andersson, Jennie, 1978, et al.
(författare)
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Eosinophils from hematopoietic stem cell recipients suppress allogeneic T cell proliferation.
- 2014
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Ingår i: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. - : Elsevier BV. - 1523-6536. ; 20:12, s. 1891-8
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophilia has been associated with less severe graft-versus-host disease (GVHD), but the underlying mechanism is unknown. We hypothesized that eosinophils diminish allogeneic T cell activation in patients with chronic GVHD. The capacity of eosinophils derived from healthy subjects and hematopoietic stem cell (HSC) transplant recipients, with or without chronic GVHD, to reduce allogeneic T cell proliferation was evaluated using a mixed leukocyte reaction. Eosinophil-mediated inhibition of proliferation was observed for the eosinophils of both healthy subjects and patients who underwent HSC transplantation. Eosinophils from patients with and without chronic GVHD were equally suppressive. Healthy eosinophils required cell-to-cell contact for their suppressive capacity, which was directed against CD4(+) T cells and CD8(+) T cells. Neither eosinophilic cationic protein, eosinophil-derived neurotoxin, indoleamine 2,3-dioxygenase, or increased numbers of regulatory T cells could account for the suppressive effect of healthy eosinophils. Real-time quantitative PCR analysis revealed significantly increased mRNA levels of the immunoregulatory protein galectin-10 in the eosinophils of both chronic GVHD patients and patients without GVHD, as compared with those from healthy subjects. The upregulation of galectin-10 expression in eosinophils from patients suggests a stimulatory effect of HSC transplantation in itself on eosinophilic galectin-10 expression, regardless of chronic GVHD status. To conclude, eosinophils from HSC transplant recipients and healthy subjects have a T cell suppressive capacity.
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| 4. |
- Andersson Lundell, Anna-Carin, 1976, et al.
(författare)
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Development of gut-homing receptors on circulating B cells during infancy.
- 2011
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Ingår i: Clinical immunology. - : Elsevier BV. - 1521-7035 .- 1521-6616. ; 138:1, s. 97-106
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Tidskriftsartikel (refereegranskat)abstract
- B cell gut-homing is mainly mediated by α4β7, CCR9 and CCR10. We here studied the expression of these receptors on B cells from cord blood and from peripheral blood at 1, 4, 18 and 36months of age in a prospective cohort of Swedish infants. The proportion of all B cells expressing α4β7 as well as the fraction of CCR10+ B cells expressing α4β7 was highest in early infancy. Nearly all naïve B cells in all age groups expressed α4β7, whereas the expression on class-switched B cells decreased with age. Moreover, the proportion of both IgA+ and IgG+ B cells expressing α4β7, CCR9 and CCR10 were higher during the first months when compared to adults. In conclusion, the high fraction of circulating IgA+ and IgG+ B cells expressing CCR9 and CCR10 in the first months of life indicates activation of naïve B cells in the gut, coinciding with bacterial colonization.
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| 5. |
- Hennings, Viktoria, et al.
(författare)
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The presence of serum anti-SARS-CoV-2 IgA appears to protect primary health care workers from COVID-19.
- 2022
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Ingår i: European journal of immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 52:5, s. 800-809
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Tidskriftsartikel (refereegranskat)abstract
- The patterns of humoral and cellular responses to SARS-CoV-2 were studied in Swedish primary health care workers (n = 156) for 6 months during the Covid-19 pandemic. Serum IgA and IgG to SARS-CoV-2, T-cell proliferation and cytokine secretion, demographic and clinical data, PCR-verified infection, and self-reported symptoms were monitored. The multivariate method OPLS-DA was used to identify immune response patterns coupled to protection from Covid-19. Contracting Covid-19 was associated with SARS-CoV-2-specific neutralizing serum IgG, T cell, IFN-γ, and granzyme B responses to SARS-CoV-2, self-reported typical Covid-19 symptoms, male sex, higher BMI, and hypertension. Not contracting Covid-19 was associated with female sex, IgA-dominated, or no antibody responses to SARS-CoV-2, airborne allergy, and smoking. The IgG-responders had SARS-CoV-2-specific T-cell responses including a cytotoxic CD4+ T-cell population expressing CD25, CD38, CD69, CD194, CD279, CTLA-4, and granzyme B. IgA-responders with no IgG response to SARS-CoV-2 constituted 10% of the study population. The IgA responses were partially neutralizing and only seen in individuals who did not succumb to Covid-19. To conclude, serum IgG-dominated responses correlated with T-cell responses to SARS-CoV-2 and PCR-confirmed Covid-19, whereas IgA-dominated responses correlated with not contracting the infection.
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| 6. |
- Hjälmeskog, Karin, 1954-, et al.
(författare)
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Didaktik i förskolan
- 2020
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Att vara förskollärare är ett mångfacetterat och utmanande yrke som kräver kunnande inom en mängd olika områden. Det kräver också en helhetssyn på barnen där omsorg, utveckling och lärande hänger ihop. På förskolan läggs grunden för att barnen utvecklas och lär under resten av sina liv.I den här boken tas didaktik upp ur ett antal olika perspektiv. Det handlar om alla de didaktiska val förskolläraren gör, och om att se olika alternativ när man planerar och genomför undervisning. Det handlar också om att undersöka vad som sker i undervisningen, och att reflektera över det som skett och varför.I bokens olika kapitel diskuteras bland annat hur man som förskollärare kan stödja barns utveckling av ämneskunskap och hur man kan stödja barns kommunikativa förmåga, i tal och skrift. Omsorg, utveckling och lärande i vardagliga situationer i förskolan samt hur man utvecklar ett genusmedvetet förhållningssätt tas också upp.Med konkreta exempel hjälper boken blivande och verksamma förskollärare att konkretisera läroplanens mål. Förhoppningen är att både inspirera och utmana förskollärares tankar om sitt arbete, och bidra till givande diskussioner i arbetslaget.Bokens författare har tillsammans lång erfarenhet från förskola, forskning och undervisning på förskollärarprogram vid flera universitet. Bland annat verkar de nu vid Uppsala universitet och Kungliga tekniska högskolan.
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| 7. |
- Lingblom, Christine, 1984, et al.
(författare)
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Regulatory Eosinophils Suppress T Cells Partly through Galectin-10
- 2017
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 198:12, s. 4672-4681
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils have the capacity to regulate the function of T cell subsets. Our aim was to test the hypothesis of the existence of a regulatory subset of eosinophils. Human eosinophils were incubated with T cells that were stimulated with allogeneic leukocytes or CD3/ CD28 cross-linking. After 2 d of coculture, 11% of the eosinophils gained CD16 expression. A CD16(hi) subset of eosinophils, encompassing 1-5% of all eosinophils, was also identified in the blood of healthy subjects. FACS sorting showed that these CD16(hi) eosinophils were significantly stronger suppressors of T cell proliferation than were conventional CD16 neg eosinophils. Human eosinophils contain stores of the immunoregulatory protein galectin-10. We found that Ab-mediated neutralization of galectin-10 partially abrogated the suppressive function of the eosinophils. Moreover, recombinant galectin-10 by itself was able to suppress T cell proliferation. Finally, we detected galectin-10-containing immune synapses between eosinophils and lymphocytes. To conclude, we describe a subset of suppressive eosinophils expressing CD16 that may escape detection because CD16-based negative selection is the standard procedure for the isolation of human eosinophils. Moreover, we show that galectin-10 functions as a T cell-suppressive molecule in eosinophils.
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| 8. |
- Strömbeck, Anna, et al.
(författare)
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Allergic disease in 8-year old children is preceded by delayed B-cell maturation.
- 2017
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Ingår i: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 1365-2222. ; 47:7, s. 918-928
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Tidskriftsartikel (refereegranskat)abstract
- We previously reported that exposure to a farming environment is allergy-protective, while high proportions of neonatal immature/naïve CD5(+) B cells and putative regulatory T cells (Tregs) are risk factors for development of allergic disease and sensitization up to 3 years of age.To examine if B- and T-cell maturation are associated with allergic disease and farming environment over the first 8 years in life.In the prospective FARMFLORA study, including both farming and non-farming families, 48 out of 65 children took part in the 8-year follow-up study. Various B- and T-cell maturation variables were examined in blood samples obtained at several occasions from birth to 8 years of age and related to doctors' diagnosed allergic disease and sensitization, and to farming environment.We found that the incidence of allergic disease was lower among farmers' compared to non-farmers' children during the 8-years follow-up period, and that farmers' children had higher proportions of memory B cells at 8 years of age. Moreover, a high proportion of neonatal CD5(+) B cells was a risk factor for and may predict development of allergic disease at 8 years of age. A high proportion of Tregs was not protective against development of these conditions.High proportions of neonatal naïve B cells remained as a risk factor for allergic disease in school-aged children. Thus, the accelerated B-cell maturation observed among farmers' children may be crucial for the allergy-protective effect of a farming environment. This article is protected by copyright. All rights reserved.
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| 9. |
- Vasileiadis, Georgios, et al.
(författare)
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Adipocytokines in Untreated Newly Diagnosed Rheumatoid Arthritis: Association with Circulating Chemokines and Markers of Inflammation
- 2021
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Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Adiponectin, leptin, and resistin are adipocytokines whose levels are elevated in blood and synovial fluid from patients with rheumatoid arthritis (RA). However, their role in RA pathogenesis is unclear. Here, we examined whether adipocytokines are associated with circulating chemokines, markers of inflammation and RA disease activity in patients with untreated newly diagnosed RA. Plasma levels of 15 chemokines, adiponectin, leptin, and resistin were measured using flow cytometry bead-based immunoassay or enzyme-linked immunosorbent assay (ELISA) in a cohort of 70 patients with untreated newly diagnosed RA. Markers of inflammation and disease activity were also assessed in all patients. Positive association was found between total adiponectin and CXCL10 (beta = 0.344, p = 0.021), CCL2 (beta = 0.342, p = 0.012), and CXCL9 (beta = 0.308, p = 0.044), whereas high-molecular weight (HMW) adiponectin associated only with CXCL9 (beta = 0.308, p = 0.033). Furthermore, both total and HMW adiponectin were associated with C-reactive protein (beta = 0.485, p = 0.001; beta = 0.463, p = 0.001) and erythrocyte sedimentation rate (beta = 0.442, p = 0.001; beta = 0.507, p < 0.001). Leptin and resistin were not associated with plasma chemokines, markers of inflammation, or disease activity scores. Our study shows an association between circulating adiponectin and pro-inflammatory chemokines involved in RA pathogenesis as well as markers of inflammation in a well-characterized cohort of patients with untreated newly diagnosed RA.
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| 10. |
- Aldridge, Jonathan, et al.
(författare)
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Blood chemokine levels are markers of disease activity but not predictors of remission in early rheumatoid arthritis.
- 2022
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Ingår i: Clinical and experimental rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 40:7, s. 1393-1402
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Tidskriftsartikel (refereegranskat)abstract
- In early rheumatoid arthritis (eRA) plasma levels of specific chemokines have been shown to correlate with disease activity. However, it is unclear whether pre-treatment chemokine levels can predict disease remission at week 24, and it is not known how biological treatments with different modes of action affect plasma chemokine levels in patients with untreated eRA.This study included 347 Swedish patients with untreated eRA from the larger NORD-STAR randomised treatment trial. Here, eRA patients were treated with methotrexate combined with either prednisolone, anti-TNF (certolizumab-pegol), CTLA-4Ig (abatacept) or anti-IL6 receptor (tocilizumab). The primary clinical outcome was remission by clinical disease activity index (CDAI) defined as CDAI ≤ 2.8. Disease activity was assessed by CDAI, DAS28-ESR, DAS28-CRP, swollen joint counts, tender joint counts, ESR and CRP. The plasma concentrations of 14 chemokines were measured at baseline and after 24 weeks of treatment by bead-based immunoassay or ELISA.Baseline plasma concentrations of CXCL10, CXCL8, CXCL9, CXCL11, CXCL5 and CCL2 correlated with baseline disease activity measures. After 24 weeks of treatment, plasma levels of CXCL10, CXCL8, CXCL9, CXCL11 and CXCL13 decreased in all treatment groups except in patients treated with anti-IL6 receptor. In multivariate factor analysis, plasma chemokine levels at baseline could not differentiate patients who attained remission by week 24 from those who did not in any of the treatment groups.In patients with untreated eRA, plasma levels of several chemokines correlate with disease activity at baseline but cannot predict remission after 24 weeks of treatment with methotrexate combined with prednisolone, anti‑TNF, CTLA‑4Ig or anti‑IL6R.
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