1. T cell islet accumulation in type 1 diabetes is a tightly regulated, cell-autonomous event.
- Author
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Lennon GP, Bettini M, Burton AR, Vincent E, Arnold PY, Santamaria P, and Vignali DA
- Subjects
- Animals, Autoantigens immunology, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes transplantation, Diabetes Mellitus, Type 1 metabolism, Gene Transfer Techniques, Islets of Langerhans metabolism, Mice, Mice, Inbred NOD, Mice, Transgenic, T-Lymphocyte Subsets metabolism, CD4-Positive T-Lymphocytes immunology, Diabetes Mellitus, Type 1 immunology, Islets of Langerhans immunology, T-Lymphocyte Subsets immunology
- Abstract
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 bystander 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.
- Published
- 2009
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