| 1. |
- Amu, Sylvie, 1978, et al.
(author)
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B-cell CD25 expression in murine primary and secondary lymphoid tissue
- 2006
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In: Scand J Immunol. - : Wiley. - 0300-9475. ; 64:5, s. 482-92
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Journal article (peer-reviewed)abstract
- B cells are in analogy with T cells capable of expressing functional IL-2 receptors. IL-2R alpha-chain (CD25) positive T cells have been studied in detail but not much is known about CD25 positive B cells. The aim of this study was to examine the phenotypic properties of the CD25 expressing B cells collected from different lymphoid organs in mice. Samples were stained for various cell surface markers and analysed using flow cytometry. We found that approximately 49% of B cells in bone marrow, 16% in peritoneal cavity, 2% in spleen and 1% in lymph nodes express CD25. In contrast, CD25 expressing B cells were not found in the blood or in Peyer's patches. Phenotypic characterization showed that CD25+ B cells in spleen, lymph nodes and peritoneal cavity have higher expression of AA4.1, CD5, CD69, CD80, CD86, CD122, CD132, IgA, IgG and IgM on their surface in comparison with CD25- B cells. In contrast, expression of IgD and IA-IE was lower on CD25+ B cells in spleen and lymph nodes. In bone marrow, the expression of CD5, CD80, CD86, CD122, CD132, IgA, IgD and IgM was lower, while the expression of AA4.1, IgG and IA-IE was increased on CD25+ B cells compared with CD25- B cells. In conclusion, our results indicate that B cells expressing CD25 are phenotypically distinctly different from those that are CD25 negative. Our findings suggest that CD25+ B cells are more prone to efficient antigen presentation and display a more mature phenotype.
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| 2. |
- Amu, Sylvie, 1978, et al.
(author)
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CD25-expressing B-lymphocytes in rheumatic diseases
- 2007
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In: Scand J Immunol. - : Wiley. - 0300-9475. ; 65:2, s. 182-91
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Journal article (peer-reviewed)abstract
- B cells play an important role in the development of autoimmune diseases due to their production of autoantibodies, antigen-presenting capacity and production of pro-inflammatory cytokines. The purpose of the present study was to analyse B cells from rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients, with respect to their expression of the IL-2 receptor (IL-2R) subunit CD25. Using flow cytometry, we found that CD25(+) B cells from RA patients expressed significantly higher frequencies of CD122 and CD132 than CD25(+) B cells from control subjects, indicating a fully functional IL-2R. These CD25(+) B cells also expressed higher frequencies of the co-stimulatory molecule CD80, whereas IgM and IgA expression was decreased compared with CD25(+) B cells from healthy controls. In addition B cells from SLE patients co-expressed CD25 together with CD80, CD122, and CD132, but to a lower degree IgD and IgM, when compared with healthy controls. Taken together, our results indicate that CD25(+) B cells from RA and SLE patients are in a highly activated state, display a more mature phenotype and suggest that this B cell subset may be involved in the pathogenesis of RA and SLE.
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| 3. |
- Amu, Sylvie, 1978, et al.
(author)
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Cytokines in the placenta of Pakistani newborns with and without intrauterine growth retardation
- 2006
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In: Pediatr Res. ; 59:2, s. 254-8
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Journal article (peer-reviewed)abstract
- Although intrauterine growth retardation (IUGR) is a major risk factor for increased neonatal mortality and morbidity, the mechanisms behind it are not clear. We analyzed cytokine gene expression and gene polymorphisms in infants with and without IUGR in Pakistan, where IUGR is very common. 45 IUGR and 55 control mother/infant pairs were studied. mRNA for IL-10, IL-8, TNF-alpha, TGF-beta, IL-6, IL-4, IL-1beta, IL-12, IFN-gamma and GAPDH was quantified with RT-PCR from placenta. Cytokine and cytokine receptor gene polymorphisms for -1087IL10, -308TNFA, -174IL6, +915TGFB1, intron 2 IL1RN, +36TNFR1, 150V IL4RA and -159CD14 were determined from genomic DNA. The serum levels of IL-1beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha and TGF-beta were measured. There was a significant decrease of IL-10 and IL-12, but increase of TGF-beta in the decidua and similarly decrease of IL-10, but increase of TGF-beta in the trophoblasts of the IUGR placentas compared with the non-IUGR placentas. We found significantly lower levels of IL-1beta in serum from the mothers of the IUGR infants and of TGF-beta in serum of the infants with IUGR compared with the non-IUGR infants. We note that the IL-10 mRNA expression in the decidua was down-regulated, but the TGF-beta mRNA up-regulated in IUGR placentas of mothers from a population with multiple risk factors for IUGR. We propose that the low IL-10 in the placenta may be involved in the pathogenesis of IUGR and might possibly be treatable.
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| 4. |
- Amu, Sylvie, 1978, et al.
(author)
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Phenotype and function of CD25-expressing B lymphocytes isolated from human umbilical cord blood.
- 2011
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In: Clinical & developmental immunology. - : Hindawi Limited. - 1740-2530 .- 1740-2522. ; 2011
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Journal article (peer-reviewed)abstract
- We have shown that approximately 30% of human peripheral blood B-cells express CD25. B cells expressing CD25 display a mature phenotype belonging to the memory B-cell population and have a better proliferative and antigen-presenting capacity. The aim of the present study was to characterize the CD25-expressing subset of B cells in human cord blood.
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| 5. |
- Amu, Sylvie, 1978, et al.
(author)
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The Human Immunomodulatory CD25(+) B Cell Population belongs to the Memory B Cell Pool
- 2007
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In: Scand J Immunol. - 0300-9475. ; 66:1, s. 77-86
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Journal article (peer-reviewed)abstract
- We have shown that human CD20(+)25(+) B cells display immunomodulatory properties. The aim of this study was to investigate if CD25(+) B cells are found within the CD27 memory B cell population, and to analyse pattern of their cytokine production. B cells isolated from healthy subjects, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients were analysed regarding the frequency of CD25(+) B cells within certain B cell subsets. Purified CD25(+) B cells from healthy subject were used in vitro to evaluate their production of immunomodulatory cytokines. In healthy subjects the majority (60%) of memory B cells (CD20(+)27(+)) also co-expressed CD25 while only 10-20% of the naive B cells (CD20(+)27(-)) and plasmablasts (CD20-27(+)) expressed CD25. In RA and SLE patients, we found that 51% and 48%, respectively, co-expressed CD25 in the memory population, whereas only 11% and 9% co-expressed CD25 in the naive B cell population. Phenotypic analysis of the CD20(+)25(+)27(+) and CD20(+)25(+)27(-) cells using CD10, CD24, CD38, CD45, CD71, CD80, CD86, CD95, CD138, BAFF-R, TACI, IgA, IgD, IgG and IgM showed that CD20(+)25(+)27(+) B cells preferentially represent highly activated, Ig class switched memory B cells. Cytokine profile analysis showed that CD25(+) B cells secreted significantly higher levels of IL-10 versus CD25(-) B cells. In contrast, TGF-beta1 secretion was similar between the CD25(+) and CD25(-) sub-populations. In conclusion, CD20(+)25(+) B cells constitute a unique subpopulation preferentially occurring among CD20(+)27(+) memory B cells. We suggest that CD25 can be used as a marker for a memory B cell subset.
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| 6. |
- Brisslert, Mikael, 1974, et al.
(author)
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Intra-peritoneal sRAGE treatment induces alterations in cellular distribution of CD19(+), CD3 (+) and Mac-1 (+) cells in lymphoid organs and peritoneal cavity.
- 2013
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In: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 351:1, s. 139-48
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Journal article (peer-reviewed)abstract
- Receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that binds a variety of pro-inflammatory ligands. Its soluble form, sRAGE, can compete for ligand binding and thereby have an anti-inflammatory effect. We have recently reported that sRAGE also exerts pro-inflammatory and chemotactic properties suggesting a dual role for sRAGE in immune modulation. Our present aim was to analyse the immunomodulatory properties of sRAGE in vivo with respect to acquired immunity. Naive mice were treated intra-peritoneally with sRAGE and cells from peritoneal lavage, spleens and bone marrow were examined. Mice treated with sRAGE displayed an increased leucocyte count in the peritoneal cavity, enlarged spleens and increased cellularity compared with vehicle-treated animals. Furthermore, sRAGE-treated mice had a significantly increased frequency and number of CD19(+) B cells in spleen and a reduced frequency of CD19(+) B cells in bone marrow compared with controls. Functionally, splenocytes from sRAGE-treated mice showed elevated IgG production and up to a four-fold increased IgM secretion compared with control animals and produced significantly higher levels of interleukin-10, interferon-γ and interleukin-6 in response to lipopolysaccharide stimulation. Our results suggest that sRAGE has immunomodulatory properties, since intra-peritoneal administration of sRAGE into healthy mice leads to rearrangements in cellular composition in the bone marrow and spleen. Moreover, the administration of sRAGE directs B cells into the spleen and towards differentiation. Our novel findings indicate that sRAGE exerts an effect on the cells of adaptive immunity.
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| 7. |
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| 8. |
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| 9. |
- Jin, Tao, 1973, et al.
(author)
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Impact of short-term therapies with biologics on prothrombotic biomarkers in rheumatoid arthritis.
- 2009
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In: Clinical and experimental rheumatology. - 0392-856X. ; 27:3, s. 491-4
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Journal article (peer-reviewed)abstract
- BACKGROUND: Imbalance of haemostasis in patients with rheumatoid arthritis (RA) contributes to future risk of cardiovascular diseases (CVD). Prothrombotic molecules, e.g. fibrinogen, D-dimer, and tPA are elevated in plasma of RA patients, being associated to CVD. There is no imformation about the influence of biological drugs, e.g. anti-CD20 and tumor necrosis factor (TNF) antibodies on these prothrombotic molecules. OBJECTIVE: To assess whether anti-TNF and anti-CD20 therapies modify the profiles of cardiovascular risk factors in patients with RA. METHODS: The expression of prothrombotic molecules in plasma was investigated in 10 RA patients before and after treatment with TNF-alpha antibodies and in another 12 RA patients before and after anti-CD20 treatment. RESULTS: Both anti-TNF and anti-CD20 infusions gave rise to clear clinical improvement. However, only anti-CD20 infusion significantly (p=0.05) reduced concentration of fibrinogen (p=0.05), D-dimer (p<0.001), as well as tPA levels (p<0.01). In contrast, in TNF antibody treated patients only tPA levels were significantly decreased following the treatment (p<0.05). CONCLUSIONS: Infusion of CD20 antibodies to the patients with active RA led to a clearly reduced plasma levels of predictors of CVD indicating that this treatment, apart from its anti-inflammatory properties, may reduce the risk for future CVD in RA.
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| 10. |
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| 11. |
- Nasi, Aikaterini, et al.
(author)
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Dendritic cell response to HIV-1 is controlled by differentiation programs in the cells and strain-specific properties of the virus
- 2017
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8:MAR
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Journal article (peer-reviewed)abstract
- Dendritic cells (DCs) are potent antigen-presenting cells that might play contradictory roles during HIV-1 infection, contributing not only to antiviral immunity but also to viral dissemination and immune evasion. Although DCs are characterized by enormous functional diversity, it has not been analyzed how differentially programmed DCs interact with HIV-1. We have previously described the reprogramming of DC development by endogenously produced lactic acid that accumulated in a cell culture density-dependent manner and provided a long-lasting anti-inflammatory signal to the cells. By exploiting this mechanism, we generated immunostimulatory DCs characterized by the production of TH1 polarizing and inflammatory mediators or, alternatively, suppressed DCs that produce IL-10 upon activation, and we tested the interaction of these DC types with different HIV-1 strains. Cytokine patterns were monitored in HIV-1-exposed DC cultures. Our results showed that DCs receiving suppressive developmental program strongly upregulated their capacity to produce the TH1 polarizing cytokine IL-12 and the inflammatory chemokines CCL2 and CCL7 upon interaction with HIV-1 strains IIIB and SF162. On the contrary, HIV-1 abolished cytokine production in the more inflammatory DC types. Preincubation of the cells with the HIV-1 proteins gp120 and Nef could inhibit IL-12 production irrespectively of the tested DC types, whereas MyD88- and TRIF-dependent signals stimulated IL-12 production in the suppressed DC type only. Rewiring of DC cytokines did not require DC infections or ligation of the HIV-1 receptor CD209. A third HIV-1 strain, BaL, could not modulate DC cytokines in a similar manner indicating that individual HIV-1 strains can differ in their capacity to influence DCs. Our results demonstrated that HIV-1 could not induce definite and invariable modulatory programs in DCs. Instead, interaction with the virus triggered different responses in different DC types. Thus, the outcome of DC-HIV-1 interactions might be highly variable, shaped by endogenous features of the cells and diversity of the virus.
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| 12. |
- Rehnberg, Maria, 1984, et al.
(author)
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Short- and long-term effects of anti-CD20 treatment on B cell ontogeny in bone marrow of patients with rheumatoid arthritis.
- 2009
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In: Arthritis research & therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 11:4
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Journal article (peer-reviewed)abstract
- INTRODUCTION: In the present study we evaluated changes in the B cell phenotype in peripheral blood and bone marrow (BM) of patients with rheumatoid arthritis (RA) following anti-CD20 treatment using rituximab. METHODS: Blood and BM samples were obtained from 37 patients with RA prior to rituximab treatment. Ten of these patients were resampled 1 month following rituximab, 14 patients after 3 months and the remaining 13 patients were included in the long-term follow up. B cell populations were characterized by CD27/IgD/CD38/CD24 expression. RESULTS: One and three months following rituximab BM retained up to 30% of B cells while circulation was totally depleted of B cells. Analysis of the remaining BM B cells showed prevalence of immature and/or transitional B cells (CD38++CD24++) and CD27+IgD- memory cells, while IgD+ cells were completely depleted. A significant reduction of CD27+ cells in BM and in circulation was observed long after rituximab treatment (mean 22 months), while levels of naive B cells in BM and in circulation were increased. The levels of rheumatoid factor decline after rituximab treatment but returned to baseline levels at the time of retreatment. CONCLUSIONS: Anti-CD20 treatment achieves a depletion of IgD+ B cells shortly after the treatment. At the long term follow up, a reduction of CD27+ B cells was observed in blood and BM. The prolonged inability to up-regulate CD27 may inhibit the renewal of memory B cells. This reduction of CD27+ B cells does not prevent autoantibody production suggesting that mechanisms regulating the formation of auto reactive clones are not disrupted by rituximab.
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| 13. |
- Rehnberg, Maria, 1984, et al.
(author)
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Vaccination response to protein and carbohydrate antigens in patients with rheumatoid arthritis after rituximab treatment.
- 2010
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In: Arthritis research & therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 12:3
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Rheumatoid arthritis (RA) is frequently complicated with infections. The aim of our study was to evaluate vaccination response in patients with RA after B-cell depletion by using rituximab. METHODS: Influenza (Afluria) and pneumococcal polysaccharides (Pneumo23) vaccines were given 6 months after rituximab (post-RTX group, n=11) or 6 days before rituximab treatment (pre-RTX group; n=8). RA patients never exposed to RTX composed the control group (n=10). Vaccine-specific cellular responses were evaluated on day 6 after vaccination, and vaccine-specific humoral responses, on day 21. RESULTS: On day 6 after vaccination, formation of influenza-specific B cells was lower in post-RTX group as compared with the pre-RTX group and controls (P=0.04). Polysaccharide-specific B cells were found in 27% to 50%, being equally distributed between the groups. On day 21, the impairment of humoral responses was more pronounced with respect to influenza as compared with the pneumococcal vaccine and affected both IgG and light-chain production. Total absence of influenza-specific IgG production was observed in 55% of the post-RTX group. CONCLUSIONS: RTX compromises cellular and humoral vaccine responses in RA patients. However, repeated RTX treatment or previous anti-tumor necrosis factor (anti-TNF) treatment did not accentuate these defects.
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| 14. |
- Strandberg, Louise, 1981, et al.
(author)
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Mice chronically fed high-fat diet have increased mortality and disturbed immune response in sepsis.
- 2009
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:10
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Journal article (peer-reviewed)abstract
- BACKGROUND: Sepsis is a potentially deadly disease that often is caused by gram-positive bacteria, in particular Staphylococcus aureus (S. aureus). As there are few effective therapies for sepsis, increased basic knowledge about factors predisposing is needed. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of this study was to study the effect of Western diet on mortality induced by intravenous S. aureus inoculation and the immune functions before and after bacterial inoculation. Here we show that C57Bl/6 mice on high-fat diet (HFD) for 8 weeks, like genetically obese Ob/Ob mice on low-fat diet (LFD), have increased mortality during S. aureus-induced sepsis compared with LFD-fed C57Bl/6 controls. Bacterial load in the kidneys 5-7 days after inoculation was increased 10-fold in HFD-fed compared with LFD-fed mice. At that time, HFD-fed mice had increased serum levels and fat mRNA expression of the immune suppressing cytokines interleukin-1 receptor antagonist (IL-1Ra) and IL-10 compared with LFD-fed mice. In addition, HFD-fed mice had increased serum levels of the pro-inflammatory IL-1beta. Also, HFD-fed mice with and without infection had increased levels of macrophages in fat. The proportion and function of phagocytosing granulocytes, and the production of reactive oxygen species (ROS) by peritoneal lavage cells were decreased in HFD-fed compared with LFD-fed mice. CONCLUSIONS: Our findings imply that chronic HFD disturb several innate immune functions in mice, and impairs the ability to clear S. aureus and survive sepsis.
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| 15. |
- Sylvie, Amu, 1978
(author)
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The expression and function of CD25 B cells in man and in mice
- 2008
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Doctoral thesis (other academic/artistic)abstract
- B cells play an important role both in the physiology and pathology of immune responses by production of antibodies, cytokines and by presentation of antigens. It has been shown that human CD25 expressing B cells display a mature phenotype, perform better as antigen presenting cells but secrete less immunoglobulins. The aim of this thesis was to investigate human CD25 expressing B cells phenotypically, not only in healthy individuals but also in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Further, we have also studied the phenotype and function of CD25 expressing B cells in mice. Our results from human studies show that CD25+ B cells display a highly mature and activated phenotype. These cells show high expression of IgA, IgG and CD80, and low expression of IgD and IgM both in healthy individuals and in RA patients when compared to CD25- B cells. CD25+ B cells from SLE patients did not show any difference in IgA and IgG expression but did expressed higher levels of the costimulatory molecule CD80 when compared to CD25- B cells. Furthermore, we have shown that 60% of CD27+ B cells in healthy controls, 51% in RA and 48% in SLE patients coexpress CD25, suggesting that CD25+ B cells belong to the memory B cell population. Finally, CD25+ B cells were able to produce IL-10 in much higher levels than CD25- B cells. In mice, CD25 expressing B cells from secondary lymphoid organs showed a mature and activated phenotype, high expression of the costimulatory molecules CD80 and CD86, in addition to IgA, IgG, and the early activation marker CD69. Functionally these B cells were efficient alloantigen presenting cells, they spontaneously secreted high levels of immunoglobulins of the IgA, IgG and IgM classes, were able to become antigen specific antibody secreting cells and produced high levels of different cytokines including IL-4, IL-6, IL-10, and IFN-?. In conclusion, we have shown that human CD25 expressing B cells display a highly mature and activated phenotype and belong to memory B cell subset. Also, in mice there was a clear difference both phenotypically and functionally between the CD25+ versus CD25- B cells. These data suggest that CD25 expressing B cells play a major role not just in the physiology of the immune system but also may participate in the pathogenesis of autoimmunity.
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