Publications by authors named "Arie J Stoppelenburg"

4 Publications

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Elevated Th17 response in infants undergoing respiratory viral infection.

Am J Pathol 2014 May 17;184(5):1274-9. Epub 2014 Mar 17.

Center for Molecular and Cellular Intervention, Department of Pediatric Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address:

IL-17 and T-helper (Th)17 cells contribute to viral airway pathology in human newborns. Because umbilical cord blood T cells fail to differentiate toward the Th17 lineage in the presence of autologous antigen-presenting cells, we asked whether Th17 cells are present in young infants that experience respiratory viral infection. To this end, we analyzed tracheal aspirate samples from infant patients suffering from acute respiratory syncytial virus (RSV) infection and healthy infant controls. Acute RSV infection associates with elevated IL-17 and accumulation of CD161(+) T cells in acute RSV infected lungs. Correspondingly, local Th17 polarizing cytokines were increased. In peripheral blood, we show that Th17 cells are absent in healthy 1-month-old infants, but are present in acute RSV patients. The triggering of pathogen-associated pattern receptors TLR4 and TLR7 promotes the generation of a Th17-polarizing cytokine environment by 1-month-old infant dendritic cell (DC). We thus conclude that although Th17 cells are absent in healthy newborns, Th17 cells are present in peripheral blood and the airways of infants that experience viral infection, thereby contributing to airway immunopathology.
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http://dx.doi.org/10.1016/j.ajpath.2014.01.033DOI Listing
May 2014

Defective TH17 development in human neonatal T cells involves reduced RORC2 mRNA content.

J Allergy Clin Immunol 2013 Sep 29;132(3):754-756.e3. Epub 2013 May 29.

Department of Pediatric Immunology, Center for Molecular and Cellular Intervention CMCI, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.

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http://dx.doi.org/10.1016/j.jaci.2013.04.014DOI Listing
September 2013

Hiding lipid presentation: viral interference with CD1d-restricted invariant natural killer T (iNKT) cell activation.

Viruses 2012 Oct 23;4(10):2379-99. Epub 2012 Oct 23.

Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.

The immune system plays a major role in protecting the host against viral infection. Rapid initial protection is conveyed by innate immune cells, while adaptive immunity (including T lymphocytes) requires several days to develop, yet provides high specificity and long-lasting memory. Invariant natural killer T (iNKT) cells are an unusual subset of T lymphocytes, expressing a semi-invariant T cell receptor together with markers of the innate NK cell lineage. Activated iNKT cells can exert direct cytolysis and can rapidly release a variety of immune-polarizing cytokines, thereby regulating the ensuing adaptive immune response. iNKT cells recognize lipids in the context of the antigen-presenting molecule CD1d. Intriguingly, CD1d-restricted iNKT cells appear to play a critical role in anti-viral defense: increased susceptibility to disseminated viral infections is observed both in patients with iNKT cell deficiency as well as in CD1d- and iNKT cell-deficient mice. Moreover, viruses have recently been found to use sophisticated strategies to withstand iNKT cell-mediated elimination. This review focuses on CD1d-restricted lipid presentation and the strategies viruses deploy to subvert this pathway.
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http://dx.doi.org/10.3390/v4102379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3497057PMC
October 2012

Endosomal processing for antigen presentation mediated by CD1 and Class I major histocompatibility complex: roads to display or destruction.

Immunology 2009 Jun;127(2):163-70

Department of Pediatric Immunology, University Medical Center Utrecht, Wilhelmina Children's Hospital, the Netherlands.

The presentation of antigen in a form that can be recognized by T lymphocytes of the immune system requires antigen processing and association of antigen-derived fragments with molecules encoded by the major histocompatibility complex (MHC) locus or by the CD1 locus. Much emphasis on antigen processing and presentation in the last decades has focused on what we consider 'conventional routes' of antigen processing and presentation, whereby extracellular antigens are processed for presentation via Class II MHC complexes and cytosolic antigens are presented as peptide-Class I MHC complexes. We here highlight two other pathways in myeloid dendritic cells, those of lipid antigen presentation in association with CD1 and of peptide cross-presentation via Class I MHC complexes. Some pathogens evade immune recognition through inhibition of antigen presentation of phagosomal origin. Deviations in endosomal antigen processing and presentation are also seen in individuals suffering from glycosphingolipid lysosomal lipid storage diseases. We summarize recent developments in the endosomal antigen processing and presentation pathway, for display as lipid-CD1 complexes to natural killer T cells and as peptide-Class I MHC complexes to CD8 T cells.
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http://dx.doi.org/10.1111/j.1365-2567.2009.03078.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2691781PMC
June 2009