Faculty Collaboration Database

Activated NKT cells inhibit autoimmune diabetes through tolerogenic recruitment of dendritic cells to pancreatic lymph nodes. J Immunol 2005 Feb 01;174(3):1196-204

Date

01/22/2005

Pubmed ID

15661873

DOI

10.4049/jimmunol.174.3.1196

Scopus ID

2-s2.0-19944431804 (requires institutional sign-in at Scopus site)   123 Citations

Abstract

NKT cell activation by alpha-galactosylceramide (alpha-GalCer) inhibits autoimmune diabetes in NOD mice, in part by inducing recruitment to pancreatic lymph nodes (PLNs) of mature dendritic cells (DCs) with disease-protective effects. However, how activated NKT cells promote DC maturation, and what downstream effect this has on diabetogenic T cells was unknown. Activated NKT cells were found to produce a soluble factor(s) inducing DC maturation. Initially, there was a preferential accumulation of mature DCs in the PLNs of alpha-GalCer-treated NOD mice, followed by a substantial increase in T cells. Adoptive transfer of a diabetogenic CD8 T cell population (AI4) induced a high rate of disease (75%) in PBS-treated NOD recipients, but not in those pretreated with alpha-GalCer (8%). Significantly, more AI4 T cells accumulated in PLNs of alpha-GalCer than PBS-treated recipients, while no differences were found in mesenteric lymph nodes from each group. Compared with those in mesenteric lymph nodes, AI4 T cells entering PLNs underwent greater levels of apoptosis, and the survivors became functionally anergic. NKT cell activation enhanced this process. Hence, activated NKT cells elicit diabetes protection in NOD mice by producing a soluble factor(s) that induces DC maturation and accumulation in PLNs, where they subsequently recruit and tolerize pathogenic T cells.

Author List

Chen YG, Choisy-Rossi CM, Holl TM, Chapman HD, Besra GS, Porcelli SA, Shaffer DJ, Roopenian D, Wilson SB, Serreze DV

Author

Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adjuvants, Immunologic
Animals
B-Lymphocyte Subsets
CD8-Positive T-Lymphocytes
Cell Aggregation
Cell Differentiation
Cell Movement
Cell Proliferation
Cells, Cultured
Clone Cells
Dendritic Cells
Diabetes Mellitus, Type 1
Female
Galactosylceramides
Immune Tolerance
Killer Cells, Natural
Lymph Nodes
Lymphocyte Activation
Male
Mice
Mice, Inbred NOD
Mice, Knockout
Pancreas
Solubility
T-Lymphocyte Subsets