Open AccessThe Autoimmune Diabetes LocusIdd9Regulates Development of Type 1 Diabetes by Affecting the Homing of Islet-Specific T Cells
Author(s) -
Hanspeter Waldner,
Raymond A. Sobel,
Nichole N. Price,
Vijay K. Kuchroo
Publication year - 2006
Publication title -
the journal of immunology/the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.176.9.5455
Subject(s) - insulitis , nod mice , islet , biology , homing (biology) , endocrinology , medicine , diabetes mellitus , adoptive cell transfer , immunology , type 1 diabetes , immune system , t cell , ecology
Several genetic insulin-dependent diabetes (Idd) intervals that confer resistance to autoimmune diabetes have been identified in mice and humans, but the mechanisms by which they protect against development of diabetes have not been elucidated. To determine the effect of Idd9 on the function of islet-specific T cells, we established novel BDC-Idd9 mice that harbor BDC2.5 TCR transgenic T cells containing the Idd9 of diabetes-resistant B10 mice. We show that the development and functional responses of islet-specific T cells from BDC-Idd9 mice are not defective compared with those from BDC mice, which contain the Idd9 of diabetes-susceptible NOD mice. Upon transfer, BDC T cells rapidly induced severe insulitis and diabetes in NOD.scid mice, whereas those from BDC-Idd9 mice mediated a milder insulitis and induced diabetes with a significantly delayed onset. BDC and BDC-Idd9 T cells expanded comparably in recipient mice. However, BDC-Idd9 T cells accumulated in splenic periarteriolar lymphatic sheaths, whereas BDC T cells were mainly found in pancreatic lymph nodes and pancreata of recipients, indicating that the transferred T cells differed in their homing. We provide evidence that the migration pattern of transferred BDC and BDC-Idd9 T cells at least partly depends on their differential chemotaxis toward the CCR7 ligand CCL19. Taken together, our data show that the Idd9 locus regulates development of type 1 diabetes by affecting the homing of islet-specific T cells.