Autoreactive T cell trafficking into pancreatic islets during type 1 diabetes is more permissive as infiltration increases and requires CD11c+ APCs. (CAM4P.153)

Type 1 diabetes (T1D) is a largely T cell mediated autoimmune disease that destroys the β-cells of the pancreatic islets. While initiation of disease requires T cell activation in the pancreatic lymph node, T cells must enter the islets to destroy β-cells. To investigate mechanisms required for T cell entry into the islets we established an intra-vital 2-photon pancreas imaging technique in the non-obese diabetic mouse. We determined that extravasation into the pancreatic islets is an extended process compared to lymph node entry, averaging 47 minutes from T cell arrest to completion of extravasation in islets with advanced T cell infiltration. Entry was more restricted at earlier stages of infiltration, with a duration of extravasation longer than our observation period of 2 hours. T cell entry into the islets was dependent on CD11c+ antigen presenting cells (APCs) in the islets. T cells transferred prior to CD11c+ APC depletion were able to enter the islets; while CD11c+ APC depletion prevented further entry. However, antigen was not required for entry of either activated or naive T cells, suggesting a role for CD11c+ APCs other than antigen presentation. These studies demonstrate that T cell entry requires the presence of CD11c+ APCs within the islets, and as islet infiltration increases T cell extravasation becomes less restricted. Overall, CD11c+ APCs may be a therapeutic target for treatment of T1D by preventing T cell entry into remaining or transplanted islets.