Interleukin-21 receptor-mediated signals control autoreactive T cell infiltration in pancreatic islets

It remains unclear how interleukin-21 receptor (IL-21R) contributes to type 1 diabetes. Here we have shown that dendritic cells (DCs) in the pancreas required IL-21R not for antigen uptake, but to acquire the chemokine receptor CCR7 and migrate into the draining lymph node. Consequently, less antige...

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Veröffentlicht in:Immunity (Cambridge, Mass.) Jg. 36; H. 6; S. 1060
Hauptverfasser: Van Belle, Tom L, Nierkens, Stefan, Arens, Ramon, von Herrath, Matthias G
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 29.06.2012
Schlagworte:
Adoptive Transfer
Animals
Antigen Presentation
Autoimmunity - immunology
CD4-Positive T-Lymphocytes - immunology
CD40 Antigens - immunology
CD40 Ligand - immunology
CD8-Positive T-Lymphocytes - immunology
Chemotaxis, Leukocyte
Diabetes Mellitus, Type 1 - immunology
Diabetes Mellitus, Type 1 - pathology
Disease Models, Animal
Disease Resistance
Interleukin-21 Receptor alpha Subunit - deficiency
Interleukin-21 Receptor alpha Subunit - genetics
Interleukin-21 Receptor alpha Subunit - physiology
Islets of Langerhans - immunology
Lymph Nodes - immunology
Lymph Nodes - pathology
Lymphocyte Activation
Lymphocyte Cooperation
Lymphocytic choriomeningitis virus
Mice
Mice, Inbred NOD
Receptors, CCR7 - metabolism
Specific Pathogen-Free Organisms
Spleen - immunology
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - transplantation
ISSN:1097-4180, 1097-4180
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Zusammenfassung:It remains unclear how interleukin-21 receptor (IL-21R) contributes to type 1 diabetes. Here we have shown that dendritic cells (DCs) in the pancreas required IL-21R not for antigen uptake, but to acquire the chemokine receptor CCR7 and migrate into the draining lymph node. Consequently, less antigen, major histocompatibility complex (MHC) class II, and CD86 was provided to autoreactive effector cells in Il21r(-/-) mice, impairing CD4(+) T cell activation, CD40:CD40L interactions, and pancreatic infiltration by autoreactive T cells. CD40 crosslinking restored defective CD4(+) cell expansion and CD4 independently expanded autoreactive CD8(+) cells, but CD8(+) cells still required CD4(+) cells to reach the pancreas and induce diabetes. Diabetes induction by transferred T cells required IL-21R-sufficient host antigen-presenting cells. Transferring IL-21R-sufficient DCs broke diabetes resistance in Il21r(-/-) mice. We conclude that IL-21R controls both antigen transport by DCs and the crucial beacon function of CD4(+) cells for autoreactive CD8(+) cells to reach the islets.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1097-4180
1097-4180
DOI:10.1016/j.immuni.2012.04.005