PD-1 - PD-L1 pathway is involved in suppressing alloreactivity of heart infiltrating T cells during murine GVHD across minor histocompatibility antigen barriers

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Karin Schilbach
  • Judith Schick
  • Manfred Wehrmann
  • Gernot Wollny
  • Simon Perikles
  • Paul G Schlegel
  • Matthias Eyrich
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000248381700012&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1097/01.tp.0000268074.77929.54
eISSN
1534-6080
Externe Identifier
  • Clarivate Analytics Document Solution ID: 194ZG
  • PubMed Identifier: 17667813
ISSN
0041-1337
Ausgabe der Veröffentlichung
2
Zeitschrift
TRANSPLANTATION
Schlüsselwörter
  • stem cell transplantation
  • graft-versus-host disease
  • organ specificity
  • peripheral tolerance
  • heart
  • T cells
  • PD-L1
Paginierung
214 - 222
Datum der Veröffentlichung
2007
Status
Published
Titel
PD-1 - PD-L1 pathway is involved in suppressing alloreactivity of heart infiltrating T cells during murine GVHD across minor histocompatibility antigen barriers
Sub types
  • Article
Ausgabe der Zeitschrift
84

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Autoren
  • Karin Schilbach
  • Judith Schick
  • Manfred Wehrmann
  • Gernot Wollny
  • Simon Perikles
  • Paul G Schlegel
  • Matthias Eyrich
DOI
10.1097/01.tp.0000268074.77929.54
ISSN
0041-1337
Ausgabe der Veröffentlichung
2
Zeitschrift
Transplantation
Sprache
en
Paginierung
214 - 222
Datum der Veröffentlichung
2007
Status
Published
Herausgeber
Ovid Technologies (Wolters Kluwer Health)
Herausgeber URL
http://dx.doi.org/10.1097/01.tp.0000268074.77929.54
Datum der Datenerfassung
2024
Titel
PD-1–PD-L1 Pathway Is Involved in Suppressing Alloreactivity of Heart Infiltrating T Cells During Murine GVHD Across Minor Histocompatibility Antigen Barriers
Ausgabe der Zeitschrift
84

Datenquelle: Crossref

Abstract
<h4>Background</h4>Graft-versus-host disease (GVHD) is still a major cause of morbidity and mortality after allogeneic stem cell transplantation. GVHD mainly affects skin, liver, and intestine, whereas other organs usually are spared. In the present study, we wanted to investigate whether local regulatory T cells (Treg) or differential expression of immunomodulatory molecules contribute to organ specificity of GVHD.<h4>Methods</h4>In a murine B10.D2->BALB/c (both H-2) model, GVHD was induced by transplantation of 1x10 bone marrow and 1x10 spleen cells. We compared expression of T-cell and dendritic cell markers, CD40-CD40L, various B7 family members, FoxP3, and Th1/Th2 cytokines between ileum (GVHD-target organ) and heart (nontarget organ).<h4>Results</h4>GVHD was documented by an increase of CD4 T cells with accompanying tissue destruction in ileum but not in heart. We found a significantly increased expression of PD-L1 in heart on day 14 and 21 as well as of CTLA-4 on day 21 after transplantation, whereas all other molecules were not different between heart and ileum. In heart, PD-L1 was expressed on lymphoid cells, endothelial cells, CD8alpha+CD11c+DCs, and up-regulated during GVHD. In contrast, in the ileum only endothelial cells stained weekly positive for PD-L1. Furthermore, we could not find any evidence for the presence of Tregs in the heart.<h4>Conclusions</h4>Our data indicate that immunomodulatory molecules such as PD-L1 rather than Tregs play pivotal roles in the tissue-specific regulation of alloresponses. Further studies are needed to refine the significance of the PD-L1 pathway in GVHD and its versatility for therapeutic intervention.
Addresses
  • Children's Hospital, University of Tuebingen, Tuebingen, Germany. knschilb@med.uni-tuebingen.de
Autoren
  • Karin Schilbach
  • Judith Schick
  • Manfred Wehrmann
  • Gernot Wollny
  • Perikles Simon
  • Paul G Schlegel
  • Matthias Eyrich
DOI
10.1097/01.tp.0000268074.77929.54
eISSN
1534-6080
Externe Identifier
  • PubMed Identifier: 17667813
Open access
false
ISSN
0041-1337
Ausgabe der Veröffentlichung
2
Zeitschrift
Transplantation
Schlüsselwörter
  • Myocardium
  • Ileum
  • Dendritic Cells
  • CD4-Positive T-Lymphocytes
  • Animals
  • Mice, Inbred BALB C
  • Mice
  • Heart Diseases
  • Graft vs Host Disease
  • Disease Models, Animal
  • Peptides
  • Membrane Glycoproteins
  • RNA, Messenger
  • Antigens, Differentiation
  • Antigens, CD
  • Antigens, Surface
  • Minor Histocompatibility Antigens
  • Hematopoietic Stem Cell Transplantation
  • Transplantation, Autologous
  • Polymerase Chain Reaction
  • Lymphocyte Activation
  • Gene Expression
  • Female
  • Apoptosis Regulatory Proteins
  • Basic Helix-Loop-Helix Transcription Factors
  • CTLA-4 Antigen
  • Programmed Cell Death 1 Receptor
  • B7-1 Antigen
  • B7-H1 Antigen
Sprache
eng
Medium
Print
Paginierung
214 - 222
Datum der Veröffentlichung
2007
Status
Published
Datum der Datenerfassung
2007
Titel
PD-1-PD-L1 pathway is involved in suppressing alloreactivity of heart infiltrating t cells during murine gvhd across minor histocompatibility antigen barriers.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
84

Datenquelle: Europe PubMed Central

Abstract
BACKGROUND: Graft-versus-host disease (GVHD) is still a major cause of morbidity and mortality after allogeneic stem cell transplantation. GVHD mainly affects skin, liver, and intestine, whereas other organs usually are spared. In the present study, we wanted to investigate whether local regulatory T cells (Treg) or differential expression of immunomodulatory molecules contribute to organ specificity of GVHD. METHODS: In a murine B10.D2->BALB/c (both H-2) model, GVHD was induced by transplantation of 1x10 bone marrow and 1x10 spleen cells. We compared expression of T-cell and dendritic cell markers, CD40-CD40L, various B7 family members, FoxP3, and Th1/Th2 cytokines between ileum (GVHD-target organ) and heart (nontarget organ). RESULTS: GVHD was documented by an increase of CD4 T cells with accompanying tissue destruction in ileum but not in heart. We found a significantly increased expression of PD-L1 in heart on day 14 and 21 as well as of CTLA-4 on day 21 after transplantation, whereas all other molecules were not different between heart and ileum. In heart, PD-L1 was expressed on lymphoid cells, endothelial cells, CD8alpha+CD11c+DCs, and up-regulated during GVHD. In contrast, in the ileum only endothelial cells stained weekly positive for PD-L1. Furthermore, we could not find any evidence for the presence of Tregs in the heart. CONCLUSIONS: Our data indicate that immunomodulatory molecules such as PD-L1 rather than Tregs play pivotal roles in the tissue-specific regulation of alloresponses. Further studies are needed to refine the significance of the PD-L1 pathway in GVHD and its versatility for therapeutic intervention.
Autoren
  • Karin Schilbach
  • Judith Schick
  • Manfred Wehrmann
  • Gernot Wollny
  • Perikles Simon
  • Paul G Schlegel
  • Matthias Eyrich
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/17667813
DOI
10.1097/01.tp.0000268074.77929.54
ISSN
0041-1337
Ausgabe der Veröffentlichung
2
Zeitschrift
Transplantation
Schlüsselwörter
  • Animals
  • Antigens, CD
  • Antigens, Differentiation
  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen
  • B7-H1 Antigen
  • Basic Helix-Loop-Helix Transcription Factors
  • CD4-Positive T-Lymphocytes
  • CTLA-4 Antigen
  • Dendritic Cells
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Graft vs Host Disease
  • Heart Diseases
  • Hematopoietic Stem Cell Transplantation
  • Ileum
  • Lymphocyte Activation
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred BALB C
  • Minor Histocompatibility Antigens
  • Myocardium
  • Peptides
  • Polymerase Chain Reaction
  • Programmed Cell Death 1 Receptor
  • RNA, Messenger
  • Transplantation, Autologous
Sprache
eng
Country
United States
Paginierung
214 - 222
PII
00007890-200707270-00012
Datum der Veröffentlichung
2007
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2007
Titel
PD-1-PD-L1 pathway is involved in suppressing alloreactivity of heart infiltrating t cells during murine gvhd across minor histocompatibility antigen barriers.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
84

Datenquelle: PubMed

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