| 1. |
- Adair-Kirk, TL, et al.
(author)
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A site on laminin alpha 5, AQARSAASKVKVSMKF, induces inflammatory cell production of matrix metalloproteinase-9 and chemotaxis
- 2003
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In: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 171:1, s. 398-406
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Journal article (peer-reviewed)abstract
- Several peptide sequences in laminin α1, the α-chain of laminin (Ln)-1, mediate biological responses in vitro, but Ln-1 is rare in vivo. Since Ln-5 and Ln-10, which contain the α3 and α5 chains, respectively, are the most prominent laminin heterotrimers in normal adult tissues and few functional domains in other laminin chains have been identified, we are investigating the α3 and α5 chains for biological activities. Incubation of mouse macrophages with the laminin α5 peptide AQARSAASKVKVSMKF resulted in marked increase in matrix metalloproteinase (MMP)-9 mRNA and gelatinolytic activity in the conditioned media, whereas the corresponding α3 peptide QQARDAANKVAIPMRF had no effect. AQARSAASKVKVSMKF also induced expression of MMP-14, while MMP-2, MMP-3, MMP-7, MMP-12, and MMP-13 were not induced by this peptide. Deletion analyses indicated that a minimal sequence of ASKVKVSMKF was sufficient for increasing MMP-9 expression. AQARSAASKVKVSMKF was also chemotactic for neutrophils and macrophages in vitro, and induced accumulation of neutrophils and macrophages in lung airspaces in vivo following intranasal instillation into mice. Comparable accumulation occurred in MMP-9-deficient mice, indicating that MMP-9 was not required for AQARSAASKVKVSMKF-induced inflammatory cell emigration in the lung. A scrambled version of the minimal peptide, KAKSFVMVSK, was inactive. These data indicate that laminin α5-derived peptides can induce inflammatory cell chemotaxis and metalloproteinase activity.
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| 2. |
- Akhiani, Aliasghar, 1957, et al.
(author)
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Vaccine-induced immunity against Helicobacter pylori infection is impaired in IL-18-deficient mice.
- 2004
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In: Journal of immunology. - 0022-1767. ; 173:5, s. 3348-56
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Research review (peer-reviewed)abstract
- Protective immunity against Helicobacter pylori infection in mice has been associated with a strong Th1 response, involving IL-12 as well as IFN-gamma, but recent studies have also demonstrated prominent eosinophilic infiltration, possibly linked to local Th2 activity in the gastric mucosa. In this study we investigated the role of IL-18, because this cytokine has been found to be a coregulator of Th1 development as well as involved in Th2-type responses with local eotaxin production that could influence gastric eosinophilia and resistance to infection. We found that IL-18(-/-) mice failed to develop protection after oral immunization with H. pylori lysate and cholera toxin adjuvant, indicating an important role of IL-18 in protection. Well-protected C57BL/6 wild-type (WT) mice demonstrated substantial influx of CD4(+) T cells and eosinophilic cells in the gastric mucosa, whereas IL-18(-/-) mice had less gastritis, few CD4(+) T cells, and significantly reduced numbers of eosinophilic cells. T cells in well-protected WT mice produced increased levels of IFN-gamma and IL-18 to recall Ag. By contrast, unprotected IL-18(-/-) mice exhibited significantly reduced gastric IFN-gamma and specific IgG2a Ab levels. Despite differences in gastric eosinophilic cell infiltration, protected WT and unprotected IL-18(-/-) mice had comparable levels of local eotaxin, suggesting that IL-18 influences protection via Th1 development and IFN-gamma production rather than through promoting local production of eotaxin and eosinophilic cell infiltration.
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| 3. |
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| 4. |
- Almkvist, Jenny, 1971, et al.
(author)
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Activation of the neutrophil nicotinamide adenine dinucleotide phosphate oxidase by galectin-1.
- 2002
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In: Journal of immunology (Baltimore, Md. : 1950). - 0022-1767. ; 168:8, s. 4034-4041
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Journal article (peer-reviewed)abstract
- Galectins are a group of lactose-binding proteins widely distributed in nature. Twelve mammalian galectins have so far been identified, but their functions are to a large extent unknown. In this work we study galectin-1 in its interaction with human neutrophils, with regard to both cell surface binding and activation of the superoxide-producing NADPH-oxidase. We show that galectin-1 is able to activate the neutrophil NADPH-oxidase, provided that the cells have been primed by extravasation from the blood into the tissue, an activation pattern that is similar to that of galectin-3. Using in vitro priming protocols, the galectin-1 responsiveness was found to correlate to granule mobilization and galectin-1 binding to the cells, suggesting the presence of granule-localized receptors that are up-regulated to the cell surface upon priming. By galectin-1 overlay of fractionated neutrophils we identified potential galectin-1 receptor candidates localized in the membranes of the secretory vesicle and gelatinase granules. The binding of galectin-1 and galectin-3 to neutrophil proteins was compared, as were the dose dependencies for activation by the two lectins. The results suggest that, although similarities are found between the two galectins, they appear to activate the NADPH-oxidase using different receptors. In conclusion, galectin-1 appears to have proinflammatory functions, mediated through activation of the neutrophil respiratory burst.
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| 5. |
- Anastasi, E, et al.
(author)
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Expression of activated Notch3 in transgenic mice enhances generation of T regulatory cells and protects against experimental autoimmune diabetes
- 2003
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In: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 171:9, s. 4504-4511
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Journal article (peer-reviewed)abstract
- Thymic-derived dysregulated tolerance has been suggested to occur in type 1 diabetes via impaired generation of CD4+CD25+ T regulatory cells, leading to autoimmune β cell destruction. In this study, we demonstrate that Notch3 expression is a characteristic feature of CD4+CD25+ cells. Furthermore, streptozotocin-induced autoimmune diabetes fails to develop in transgenic mice carrying the constitutively active intracellular domain of Notch3 in thymocytes and T cells. The failure to develop the disease is associated with an increase of CD4+CD25+ T regulatory cells, accumulating in lymphoid organs, in pancreas infiltrates and paralleled by increased expression of IL-4 and IL-10. Accordingly, CD4+ T cells from Notch3-transgenic mice inhibit the development of hyperglycemia and insulitis when injected into streptozotocin-treated wild-type mice and display in vitro suppressive activity. These observations, therefore, suggest that Notch3-mediated events regulate the expansion and function of T regulatory cells, leading to protection from experimental autoimmune diabetes and identify the Notch pathway as a potential target for therapeutic intervention in type 1 diabetes.
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| 6. |
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| 7. |
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| 8. |
- Assarsson, E, et al.
(author)
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CD8+ T cells rapidly acquire NK1.1 and NK cell-associated molecules upon stimulation in vitro and in vivo
- 2000
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In: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 165:7, s. 3673-3679
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Journal article (peer-reviewed)abstract
- NKT cells express both NK cell-associated markers and TCR. Classically, these NK1.1+TCRαβ+ cells have been described as being either CD4+CD8− or CD4−CD8−. Most NKT cells interact with the nonclassical MHC class I molecule CD1 through a largely invariant Vα14-Jα281 TCR chain in conjunction with either a Vβ2, -7, or -8 TCR chain. In the present study, we describe the presence of significant numbers of NK1.1+TCRαβ+ cells within lymphokine-activated killer cell cultures from wild-type C57BL/6, CD1d1−/−, and Jα281−/− mice that lack classical NKT cells. Unlike classical NKT cells, 50–60% of these NK1.1+TCRαβ+ cells express CD8 and have a diverse TCR Vβ repertoire. Purified NK1.1−CD8α+ T cells from the spleens of B6 mice, upon stimulation with IL-2, IL-4, or IL-15 in vitro, rapidly acquire surface expression of NK1.1. Many NK1.1+CD8+ T cells had also acquired expression of Ly-49 receptors and other NK cell-associated molecules. The acquisition of NK1.1 expression on CD8+ T cells was a particular property of the IL-2Rβ+ subpopulation of the CD8+ T cells. Efficient NK1.1 expression on CD8+ T cells required Lck but not Fyn. The induction of NK1.1 on CD8+ T cells was not just an in vitro phenomenon as we observed a 5-fold increase of NK1.1+CD8+ T cells in the lungs of influenza virus-infected mice. These data suggest that CD8+ T cells can acquire NK1.1 and other NK cell-associated molecules upon appropriate stimulation in vitro and in vivo.
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| 9. |
- Assarsson, E, et al.
(author)
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NK cells stimulate proliferation of T and NK cells through 2B4/CD48 interactions
- 2004
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In: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 173:1, s. 174-180
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Journal article (peer-reviewed)abstract
- Few studies have addressed the consequences of physical interactions between NK and T cells, as well as physical interactions among NK cells themselves. We show in this study that NK cells can enhance T cell activation and proliferation in response to CD3 cross-linking and specific Ag through interactions between 2B4 (CD244) on NK cells and CD48 on T cells. Furthermore, 2B4/CD48 interactions between NK cells also enhanced proliferation of NK cells in response to IL-2. Overall, these results suggest that NK cells augment the proliferation of neighboring T and NK cells through direct cell-cell contact. These results provide new insights into NK cell-mediated control of innate and adaptive immunity and demonstrate that receptor/ligand-specific cross talk between lymphocytes may occur in settings other than T-B cell or T-T cell interactions.
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| 10. |
- Backstrom, E, et al.
(author)
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Direct NK cell-mediated lysis of syngenic dorsal root ganglia neurons in vitro
- 2000
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In: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 165:9, s. 4895-4900
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Journal article (peer-reviewed)abstract
- In contrast to extensive studies on the role of T and B lymphocytes in the pathogenesis of autoimmune diseases of the nervous system, little is known about NK cells and their potential role in the destruction of neural tissue. NK cells have been implicated in the selective death of sympathetic neurons resident in the superior cervical ganglia of rats after exposure to the drug guanethidine. This observation suggests that NK cells may function as principle effectors in immunological diseases of the nervous system. However, the direct mechanism of action of NK cells in this model is not known. In particular, it is not known whether NK cells can kill autologous neurons directly. The aim of the present study was to examine whether NK cells can kill directly dorsal root ganglia neurons cultured in vitro. We demonstrate that C57BL/6 (B6)-derived dorsal root ganglia neurons can be killed directly by syngenic IL-2-activated NK cells, and that this nerve cell lysis is dependent on the expression of perforin in the NK cells. NK cells were less effective in destroying neurons grown in the presence of glial cells. These observations indicate a potential role for NK cells in nerve cell degeneration in inflammatory diseases of the nervous system.
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