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- Rönnelid, Johan
(författare)
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The choice of laboratory methodology influences autoantibody test results
- 2015
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- During the last 25 years, clinical autoantibody determinations have changed dramatically. Old and slow techniques with high diagnostic specificity have been replaced with automated and faster techniques that most often have a higher diagnostic sensitivity at the expense of a lower diagnostic specificity. Newer techniques are mostly quantitative, allowing for follow-up of autoantibody levels. Whereas the older procedures utilized autoantigens in soluble and native states, most modern techniques rely on autoantigens attached to surfaces, with the risk of exposure of denatured epitopes. Comparisons between antibody measurement techniques can be obtained from the results of external quality assessment programs. As the main objective for external quality assessment is the monitoring of clinical laboratories, they cannot focus on the kind of low-level and often polyreactive sera, which are common in the real world and in which a single definite target response cannot be easily defined. Such common sera are very useful, however, for analysis of differences between autoantibody measurement techniques. The European Consensus Finding Study Group on Autoantibodies has been working with this approach for 28 years.
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- Skogberg, Gabriel, et al.
(författare)
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Exosomes in the Thymus: Antigen Transfer and Vesicles.
- 2015
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Thymocytes go through several steps of maturation and selection in the thymus in order to form a functional pool of effector T-cells and regulatory T-cells in the periphery. Close interactions between thymocytes, thymic epithelial cells, and dendritic cells are of vital importance for the maturation, selection, and lineage decision of the thymocytes. One important question that is still unanswered is how a relatively small epithelial cell population can present a vast array of self-antigens to the manifold larger population of developing thymocytes in this selection process. Here, we review and discuss the literature concerning antigen transfer from epithelial cells with a focus on exosomes. Exosomes are nano-sized vesicles released from a cell into the extracellular space. These vesicles can carry proteins, microRNAs, and mRNAs between cells and are thus able to participate in intercellular communication. Exosomes have been shown to be produced by thymic epithelial cells and to carry tissue-restricted antigens and MHC molecules, which may enable them to participate in the thymocyte selection process.
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- Tauriainen, Johanna, et al.
(författare)
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Single-cell characterization of in vitro migration and interaction dynamics of T cells expanded with IL-2 and IL-7
- 2015
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- T cells are pivotal in the immune defense against cancers and infectious agents. To mount an effector response against cancer cells, T cells need to migrate to the cancer-site, engage in contacts with cancer cells, and perform their effector functions. Adoptive T cell therapy is an effective strategy as treatment of complications such as relapse or opportunistic infections after hematopoietic stem cell transplantations. This requires a sufficient amount of cells that are able to expand and respond to tumor or viral antigens. The cytokines interleukin (IL)-2 and IL-7 drive T cell differentiation, proliferation, and survival and are commonly used to expand T cells ex vivo. Here, we have used microchip-based live-cell imaging to follow the migration of individual T cells, their interactions with allogeneic monocytes, cell division, and apoptosis for extended periods of time; something that cannot be achieved by commonly used methods. Our data indicate that cells grown in IL-7 + IL-2 had similar migration and contact dynamics as cells grown in IL-2 alone. However, the addition of IL-7 decreased cell death creating a more viable cell population, which should be beneficial when preparing cells for immunotherapy.
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- Wenzel, Ulf Alexander, 1975, et al.
(författare)
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Synergy between CD40 and MyD88 does not influence host survival to Salmonella infection
- 2015
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies using purified toll-like receptor (TLR) ligands plus agonistic anti-CD40 antibodies showed that TLRs and CD40 can act synergistically on dendritic cells (DCs) to optimize T cell activation and Th1 differentiation. However, a synergistic effect of TLRs and CD40 during bacterial infection is not known. Here, we show that mice lacking the TLR adaptor MyD88 alone, or lacking both MyD88 and CD40 [double knockout (DKO) mice], are compromised in survival to Salmonella infection but have intact recruitment of neutrophils and inflammatory monocytes as well as unaltered abundance of DC subsets and DC activation in infected tissues. In contrast to infected wildtype and CD40(-/-) mice, both MyD88(-/-) mice and DKO mice lack detectable serum IFN-gamma and have elevated IL-10. A synergistic effect of TLRs and CD40 was revealed in co-culture experiments where 01-11 T cell proliferation was compromised when DKO DCs were pulsed with OVA protein and OVA(323-339) peptide, but not with heat-killed Salmonella expressing OVA (HKSOVA), relative to MyD88(-/-) DCs. By contrast, MyD88(-/-) or DKO DCs pulsed with any of the antigens had a similar ability to induce IFN-gamma that was lower than WT or CD40(-/-) DCs. DKO DCs pulsed with HKSOVA, but not with OVA or OVA(323-339), had increased IL-10 relative to MyD88(-/-) DCs. Finally, HKSHKSOVA-pulsed MyD88(-/-) and DKO DCs had similar and low induction of NF kappa B-dependent and independent genes upon co-culture with 01-11 cells. Overall, our data revealed that synergistic effects of CD40 and MyD88 do not influence host survival to Salmonella infection or serum levels of IFN-gamma or IL-10. However, synergistic effects of MyD88 and CD40 may be apparent on some (IL-10 production) but not all (01-11 proliferation and IFN-gamma production) DC functions and depend on the complexity of the antigen. Indeed, synergistic effects observed using purified ligands and well-defined antigens may not necessarily apply when complex antigens, such as live bacteria, challenge the immune system.
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