The role of liver-derived regulatory dendritic cells in prevention of type 1 diabetes.
Development of type 1 diabetes has been attributed to T-cell-mediated autoimmunity, which is regulated by antigen-presenting cells. To study the role of liver-derived B220(+) regulatory dendritic cells (DCs) in the development of diabetes in non-obese diabetic (NOD) mice, we found that liver 220(+) DCs could easily be propagated from young NOD mice, but that such propagation was extremely difficult from mice older than 11 weeks, when insulitis began. This was not simply an age-related phenomenon, because liver B220(+) DCs were readily propagated from both young and old congenic non-obese diabetic-resistant (NOR) and normal BALB/c mice. It was therefore speculated that the development of diabetes might be associated with a lack of precursors of B220(+) DC in the liver in this animal model. Unfortunately, the specific marker for precursors of liver B220(+) DC has not been identified. An alternative approach to supplement liver B220(+) DCs by intravenous administration significantly inhibited the development of diabetes by inducing T-cell hyporesponsiveness via enhancement of their apoptotic death. Liver B220(+) DCs were capable of effectively presenting antigens but, unlike plasmacytoid DCs, did not express CD11c and were not interferon-alpha producers. These observations may throw new light on the aetiopathology of type 1 diabetes.
Liang
Xiaoyan
X
Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Ma
Linlin
L
Thai
Ngoc L
NL
Fung
John J
JJ
Qian
Shiguang
S
Lu
Lina
L
D000375:Aging / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D016130:Immunophenotyping; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D013601:T-Lymphocytes / Q000276:immunology