[PDF][PDF] T cell islet accumulation in type 1 diabetes is a tightly regulated, cell-autonomous event

GP Lennon, M Bettini, AR Burton, E Vincent, PY Arnold… - Immunity, 2009 - cell.com
GP Lennon, M Bettini, AR Burton, E Vincent, PY Arnold, P Santamaria, DAA Vignali
Immunity, 2009cell.com
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 …
Summary
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.
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