T cell islet accumulation in type I diabetes is a tightly-regulated, cell-autonomous event

• Published in: Immunity (Cambridge, Mass.) Vol. 31; no. 4; pp. 643 - 653
• Main Authors: Lennon, Greig P., Bettini, Maria, Burton, Amanda R., Vincent, Erica, Arnold, Paula Y., Santamaria, Pere, Vignali, Dario A.A.
• Format: Journal Article
• Language: English
• Published: 08-10-2009
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2009.07.008

Type I 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 TCR retrogenic mice expressing two different T cell populations. By combining diabetogenic and non-diabetogenic and/or non-autoantigen specific T cells, we demonstrate that bystander T cells cannot accumulate in the pancreatic islets. Autoantigen specific T cells which accumulate in islets, but do not cause diabetes, were also unaffected by the presence of diabetogenic T cells. Additionally, 67% of TCRs cloned from 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/accumulation appears to be a cell-autonomous and tightly-regulated event and is governed by islet antigen specificity.