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Sökning: LAR1:lu > Refereegranskat > Borrebaeck Carl

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1.
  • Abayneh, Sisay A, et al. (författare)
  • Sensitivity of HIV-1 primary isolates to human anti-CD40 antibody-mediated suppression is related to co-receptor use
  • 2008
  • Ingår i: AIDS Research and Human Retroviruses. - Mary Ann Liebert, Inc.. - 1931-8405. ; 24:3, s. 447-452
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of CD40 ligation on infection by HIV-1 primary isolates with different R5 phenotypes was evaluated with a novel set of anti-CD40 monoclonal antibodies originating from a human phage display library. Five human monoclonal anti-CD40 antibodies of IgG1 subtype characterized by the ability to activate B cells via CD40 were tested for induction of the CC-chemokines RANTES and MIP-1alpha and inhibition of HIV-1 replication in primary monocyte-derived macrophages (MDM). All activating anti-CD40 antibodies were able to induce CC-chemokines in MDM. We chose the most potent antibody, clone B44, for further experiments. This antibody had a suppressive effect on HIV-1 isolates of the R5 phenotype with limited use of CCR5/CXCR4 chimeric receptors. In comparison, HIV-1 isolates with broader use of CCR5/CXCR4 chimeric receptors or with CXCR4 use were less sensitive to anti-CD40-induced suppression. The results indicate that HIV-1 replication is inhibited by human anti-CD40 monoclonal antibodies through the mechanism of CC-chemokine induction. This effect is thus restricted to HIV-1 isolates sensitive to inhibition by CC-chemokines.
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2.
  • Albrekt, Ann-Sofie, et al. (författare)
  • Skin sensitizers differentially regulate signaling pathways in MUTZ-3 cells in relation to their individual potency.
  • 2014
  • Ingår i: BMC Pharmacology. - BioMed Central. - 2050-6511. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to the recent European legislations posing a ban of animal tests for safety assessment within the cosmetic industry, development of in vitro alternatives for assessment of skin sensitization is highly prioritized. To date, proposed in vitro assays are mainly based on single biomarkers, which so far have not been able to classify and stratify chemicals into subgroups, related to risk or potency.
3.
  • Andersson, Eva, et al. (författare)
  • CD4+CD57+ T cells derived from peripheral blood do not support immunoglobulin production by B cells
  • 1995
  • Ingår i: Cellular Immunology. - Elsevier. - 0008-8749. ; 163:2, s. 245-253
  • Tidskriftsartikel (refereegranskat)abstract
    • A small subpopulation of CD4+ T cells found in peripheral blood coexpresses the CD57+ marker normally found on, e.g., NK cells. It is known that this population occurs in a higher frequency in certain diseases. The same antigen has also been shown to be expressed on CD4+ T cells derived from germinal centers. The localization of this cell population to specialized lymphoid structures suggests that it may play a role in the evolution of the antibody response following antigenic stimulation in vivo. We have examined the ability of peripheral blood helper T cells coexpressing CD57 to participate in B cell activation/differentiation and evaluated their responses to polyclonal stimulation. The CD4+CD57+ T cells do not express mRNA for a number of different cytokines or for the CD40 ligand after activation in vitro. Furthermore these cells do not induce differentiation of B cells into immunoglobulin-producing cells. Consequently, despite their CD4 phenotype and their ability to be activated, to express the IL-2 receptor, and to enter into the cell cycle, they do not act as T helper cells under conditions where CD4+/CD57- cells normally do so. The findings suggest that this peripheral blood helper T cell population is functionally different from regular CD4+ T cells. The basis for the lack of proper costimulatory signals for immunoglobulin production might be related to the low expression of CD28.
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4.
  • Andersson, Eva, et al. (författare)
  • Immunoglobulin production induced by CD57+ GC-derived helper T cells in vitro requires addition of exogenous IL-2
  • 1996
  • Ingår i: Cellular Immunology. - Elsevier. - 0008-8749. ; 169:2, s. 166-173
  • Tidskriftsartikel (refereegranskat)abstract
    • Germinal centers (GC) are well-defined areas in lymphoid organs were B cells proliferate and differentiate in response to T-cell-dependent antigens. The GC comprises B cells, follicular dendritic cells, tangible body macrophages, and a low number of CD4+ T cells. A large portion of these T cells expresses CD57. We have examined the ability of the CD4+CD57+ GC T cells to become activated and to take part in B cell activation processes, These T cells coexpress CD45RO, CD69, CD28, and upon mitogenic stimulation CD25, The cell population was found neither to containe nor to be able to produce any specific mRNA for IL-2, IL-4, and IFN-γ upon activation. Levels of mRNA encoding CD40 ligand was also undetectable under similar conditions. Furthermore, in contrast to ordinary CD4+ T cells, this population expressing CD57 was unable to induce B cells to Ig production in the presence of pokeweed mitogen or SEA unless IL-2 was added to the cultures, However, despite their apparent lack of function CD4+CD57+ GC T cells were found to rescue GC B cells from cell death in vitro to the same extent as CD4+CD57- T(h) cells, The phenotypical and functional differences found between these T cells and regular T(h)-cells suggest that they either represent a T cell subset with distinct properties within the GC yet to be determined or that they represent T cells, Irate in the immune response, having lost most of their original functions and capabilities.
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5.
  • Andréasson, Ulrika, et al. (författare)
  • B cell lymphomas express CX(3)CR1 a non-B cell lineage adhesion molecule.
  • 2008
  • Ingår i: Cancer Letters. - Elsevier. - 1872-7980. ; 259:2, s. 138-145
  • Tidskriftsartikel (refereegranskat)abstract
    • To study the differential expression of cell membrane-bound receptors and their potential role in growth and/or survival of the tumor cells, highly purified follicular lymphoma cells were analyzed, using gene expression analysis, and compared to non-malignant B cell populations. Filtering the genome for overexpressed genes coding for cell membrane-bound proteins/receptors resulted in a hit list of 27 identified genes. Among these, we have focused on the aberrant over expression of CX(3)CR1, in different types of B cell lymphoma, as compared to non-malignant B cells. We show that CX(3)CR1, which normally is not expressed on B cells, is expressed both at the mRNA and protein level in several subtypes of lymphoma. CX(3)CR1 has also shown to be involved in the homing to specific tissues that express the ligand, CX(3)CL1, in breast and prostate cancer and may thus be involved in dissemination of lymphoma.
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6.
  • Andréasson, Ulrika, et al. (författare)
  • Identification of molecular targets associated with transformed diffuse large B cell lymphoma using highly purified tumor cells.
  • 2009
  • Ingår i: American Journal of Hematology. - John Wiley & Sons. - 0361-8609. ; 84, s. 803-808
  • Tidskriftsartikel (refereegranskat)abstract
    • Follicular lymphoma (FL) frequently transforms into the more aggressive diffuse large B cell lymphoma (DLBCL-tr), but no protein biomarkers have been identified for predictive or early diagnosis. Gene expression analyses have identified genes changing on transformation but have failed to be reproducible in different studies, reflecting the heterogeneity within the tumor tissue and between tumor samples. Gene expression analyses on Affymetrix Human Genome U133 Plus 2.0 arrays were performed, using flow cytometry sorted tumor cells derived from FL and transformed DLBCL. To identify molecular targets associated with the transformation, subsequent immunohistochemistry (IHC) analyses of the corresponding proteins were performed. Using highly purified cells, this study identified 163 genes, which were significantly deregulated during the transformation in a majority of cases. Among the upregulated transcripts, 13 genes were selected for validation using IHC, based on the availability of commercial antibodies, and galectin-3 and NEK2 proteins specifically identify DLBCL-tr, when compared with FL. We demonstrate that by purifying tumor cells through cell sorting, thereby reducing the heterogeneity due to infiltrating cells, it was possible to identify distinct differences between tumor entities rather than variations due to cellular composition. Galectin-3 and NEK2 both identified a subgroup of DLBCL-tr, and the function of these protein markers also suggests a biological role in the transformation process. Am. J. Hematol. 2010. (c) 2009 Wiley-Liss, Inc.
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7.
  • Andreasson, Ulrika, et al. (författare)
  • Identification of uniquely expressed transcription factors in highly purified B-cell lymphoma samples.
  • 2010
  • Ingår i: American Journal of Hematology. - John Wiley & Sons. - 0361-8609. ; 85:6, s. 418-425
  • Tidskriftsartikel (refereegranskat)abstract
    • Transcription factors (TFs) are critical for B-cell differentiation, affecting gene expression both by repression and transcriptional activation. Still, this information is not used for classification of B-cell lymphomas (BCLs). Traditionally, BCLs are diagnosed based on a phenotypic resemblance to normal B-cells; assessed by immunohistochemistry or flow cytometry, by using a handful of phenotypic markers. In the last decade, diagnostic and prognostic evaluation has been facilitated by global gene expression profiling (GEP), providing a new powerful means for the classification, prediction of survival, and response to treatment of lymphomas. However, most GEP studies have typically been performed on whole tissue samples, containing varying degrees of tumor cell content, which results in uncertainties in data analysis. In this study, global GEP analyses were performed on highly purified, flow-cytometry sorted tumor-cells from eight subgroups of BCLs. This enabled identification of TFs that can be uniquely associated to the tumor cells of chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), hairy cell leukemia (HCL), and mantle cell lymphoma (MCL). The identified transcription factors influence both the global and specific gene expression of the BCLs and have possible implications for diagnosis and treatment.
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8.
  • Andreasson, Ulrika, et al. (författare)
  • The human IgE-encoding transcriptome to assess antibody repertoires and repertoire evolution
  • 2006
  • Ingår i: Journal of Molecular Biology. - Elsevier. - 1089-8638. ; 362:2, s. 212-227
  • Tidskriftsartikel (refereegranskat)abstract
    • Upon encounter with antigen, the B lymphocyte population responds by producing a diverse set of antigen-specific antibodies of various isotypes. The vast size of the responding populations makes it very difficult to study clonal evolution and repertoire composition occurring during these processes in humans. Here, we have explored an approach utilizing the H-EPSILON-encoding transcriptome to investigate aspects of repertoire diversity during the season of antigen exposure. We show through sequencing of randomly picked transcripts that the sizes of patients' repertoires are relatively small. This specific aspect of the transcriptome allows us to construct evolutionary trees pinpointing features of somatic hypermutation as it occurs in humans. Despite the small size of the repertoires, they are highly diverse with respect to VDJ gene usage, suggesting that the H-EPSILON-encoding transcriptome is a faithful mimic of other class-switched isotypes. Importantly, it is possible to use antibody library and selection technologies to define the specificity of clonotypes identified by random sequencing. The small size of the H-EPSILON-encoding transcriptome of peripheral blood B cells, the simple identification of clonally related sets of genes in this population, and the power of library and selection technologies ensure that this approach will allow us to investigate antibody evolution in human B lymphocytes of known specificity. As H-EPSILON repertoires show many of the hallmarks of repertoires encoding other isotypes, we suggest that studies of this type will have an impact on our understanding of human antibody evolution even beyond that occurring in the IgE-producing B cell population.
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9.
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10.
  • Borrebaeck, Carl A K, et al. (författare)
  • Does endogenous glycosylation prevent the use of mouse monoclonal antibodies as cancer therapeutics?
  • 1993
  • Ingår i: Immunology Today. - Elsevier. - 0167-5699. ; 14:10, s. 477-479
  • Tidskriftsartikel (refereegranskat)abstract
    • Monoclonal antibodies have many potential therapeutic benefits. However, when applied to humans, mouse monoclonal antibodies have several disadvantages. Here Carl Borrebaeck and colleagues describe a strategy to overcome the anti-Gal activity, thought to be one of the reasons why mouse mAbs have a limited half-life. © 1993.
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