Journal
IMMUNITY
Volume 31, Issue 4, Pages 643-653Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2009.07.008
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Funding
- Juvenile Diabetes Research Foundation International [1-2004-141, 1-2006-847]
- NIH [AI072239]
- St. Jude Cancer Center [CA-21765]
- Canadian Institutes of Health Research
- Alberta Heritage Foundation for Medical Research
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Type 1 diabetes is a T cell-mediated autoimmune disease, characterized by lymphocytic infiltration of the pancreatic islets. It is currently thought that islet antigen specificity is not a requirement for islet entry and that diabetogenic T cells can recruit a heterogeneous bystander T cell population. We tested this assumption directly by generating T cell receptor (TCR) retrogenic mice expressing two different T cell populations. By combining diabetogenic and nondiabetogenic or nonautoantigen-specific T cells, we demonstrate that by stander T cells cannot accumulate in the pancreatic islets. Autoantigen-specific T cells that accumulate in islets, but do not cause diabetes, were also unaffected by the presence of diabetogenic T cells. Additionally, 67% of TCRs cloned from nonobese diabetic (NOD) islet-infiltrating CD4(+) T cells were able to mediate cell-autonomous islet infiltration and/or diabetes when expressed in retrogenic mice. Therefore, islet entry and accumulation appears to be a cell-autonomous and tightly regulated event and is governed by islet antigen specificity.
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