Kai Scholz

Publications (4)26.98 Total impact

• Article: Virally infected mouse liver endothelial cells trigger CD8+ T-cell immunity.

  Michaela Kern, Alexey Popov, Kai Scholz, Beatrix Schumak, Dominik Djandji, Andreas Limmer, Daniela Eggle, Torsten Sacher, Rainer Zawatzky, Rafaela Holtappels, Matthias J Reddehase, Gunther Hartmann, Svenja Debey-Pascher, Linda Diehl, Ulrich Kalinke, Ulrich Koszinowski, Joachim Schultze, Percy A Knolle
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  ABSTRACT: Dendritic cell activation through ligation of pattern recognition receptors leading to full functional maturation causes induction of CD8(+) T-cell immunity through increased delivery of costimulatory signals instead of tolerance. Here we investigate whether organ-resident antigen-presenting cells, such as liver sinusoidal endothelial cells (LSECs), also switch from tolerogenic to immunogenic CD8(+) T-cell activation upon such stimulation. Murine LSECs were isolated by immunomagnetic separation and analyzed for functional maturation upon triggering pattern recognition receptors or viral infection employing gene expression analysis and T cell coculture assays. In vivo relevance of the findings was confirmed with bone-marrow chimeric animals. LSECs expressed numerous pattern recognition receptors that allowed for sentinel function, but ligand-induced activation of these receptors was not sufficient to overcome tolerance induction of CD8(+) T cells. Importantly, viral infection with murine cytomegalovirus caused functional maturation of antigen-presenting LSECs and was sufficient to promote antigen-specific differentiation into effector CD8(+) T cells in the absence of dendritic cells and independent of CD80/86. These results shed new light on the generation of organ-specific immunity and may contribute to overcoming tolerance in relevant situations, such as cancer.
  Gastroenterology 09/2009; 138(1):336-46. · 11.68 Impact Factor
• Article: Correction: Liver sinusoidal endothelial cells veto CD8 T cell activation by antigen-presenting dendritic cells.

  Frank A Schildberg, Silke I Hegenbarth, Beatrix Schumak, Kai Scholz, Andreas Limmer, Percy A Knolle
  European Journal of Immunology 07/2008; 38(6):1767. · 5.10 Impact Factor
• Article: Liver sinusoidal endothelial cells veto CD8 T cell activation by antigen-presenting dendritic cells.

  Frank A Schildberg, Silke I Hegenbarth, Beatrix Schumak, Kai Scholz, Andreas Limmer, Percy A Knolle
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  ABSTRACT: The liver is known to induce tolerance rather than immunity through tolerogenic antigen presentation or elimination of effector T cells. In particular, hepatic dendritic cells (DC) are known to be little immunogenic for CD8 T cells. Here, we investigated whether this peculiar phenotype resulted from interaction with resident hepatic cell populations. Contact of DC with liver sinusoidal endothelial cells (LSEC) but not hepatocytes or B cells vetoed antigen-presenting DC to fully activate naive CD8 T cells. This MHC-independent regulatory effect of LSEC on DC function was not connected to soluble mediators but required physical contact. Because interaction with third-party LSEC still allowed antigen-presenting DC to stimulate expression of initial activation markers on naive CD8 T cells and to stimulate activated CD8 T cells, we hypothesize that LSEC controlled the DC costimulatory function. Indeed, contact with LSEC led to reduced DC expression levels of CD80/86 or IL-12, but supplementation of these signals failed to rescue the ability to prime naive CD8 T cells, indicating involvement of further molecules. Taken together, our results reveal a novel principle operative in hepatic tolerance induction, in which LSEC not only tolerize T cells themselves but also suppress neighboring APC normally capable of inducing T cell immunity.
  European Journal of Immunology 05/2008; 38(4):957-67. · 5.10 Impact Factor
• Article: Cross-presentation of oral antigens by liver sinusoidal endothelial cells leads to CD8 T cell tolerance.

  Andreas Limmer, Jutta Ohl, Gerhard Wingender, Martina Berg, Frank Jüngerkes, Beatrix Schumak, Dominik Djandji, Kai Scholz, Alexandra Klevenz, Silke Hegenbarth, Frank Momburg, Günter J Hämmerling, Bernd Arnold, Percy A Knolle
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  ABSTRACT: After ingestion, oral antigens distribute systemically and provoke T cell stimulation outside the gastrointestinal tract. Within the liver, scavenger liver sinusoidal endothelial cells (LSEC) eliminate blood-borne antigens and induce T cell tolerance. Here we investigated whether LSEC contribute to oral tolerance. Oral antigens were efficiently cross-presented on H-2K(b) by LSEC to naive CD8 T cells. Cross-presentation efficiency in LSEC but not dendritic cells was increased by antigen-exposure to heat or low pH. Mechanistically, cross-presentation in LSEC requires endosomal maturation, involves hsc73 and proteasomal degradation. H-2K(b)-restricted cross-presentation of oral antigens by LSEC in vivo induced CD8 T cell priming and led to development of CD8 T cell tolerance in two independent experimental systems. Adoptive transfer of LSEC from mice fed with antigen (ovalbumin) into RAG2-/- knockout mice, previously reconstituted with naive ovalbumin-specific CD8 T cells, prevented development of specific cytotoxicity and expression of IFN-gamma in CD8 T cells. Using a new transgenic mouse line expressing H-2K(b) only on endothelial cells, we have demonstrated that oral antigen administration leads to tolerance in H-2K(b)-restricted CD8 T cells. Collectively, our data demonstrate a participation of the liver, in particular scavenger LSEC, in development of CD8 T cell tolerance towards oral antigens.
  European Journal of Immunology 11/2005; 35(10):2970-81. · 5.10 Impact Factor