Background: Enumeration of T cells specific for the autoantigen IGRP in peripheral blood (PB) of non-obese diabetic (NOD) mice predicts type 1 diabetes (T1D)¹ . However it is unknown whether these IGRP specific T cells are cells about to proceed to islets or whether they have exited the islets and differentiated into memory T cells. If IGRP specific T cells in PB and peripheral lymphoid tissue (PLO) have exited from the islets, their measurement could be a non-invasive biomarker of the degree of insulitis useful for predicting T1D or for monitoring immunotherapy. Islet-specific T cells can be detected in the blood of healthy and diabetic subjects, and it is difficult to differentiate the two because of the lack of access to pancreatic T cells.  If autoreactive T cells measured in PB have been to the islets and left, they should have memory T cell markers and expanded numbers compared with naïve T cells.

Aim: To study whether autoreactive T cells from the PB or PLO in NOD mice have emigrated from the islets and correlate with severity of insulitis.

Methods: Due to the low frequency of autoreactive T cells, a sensitive tetramer and magnetic enrichment was used to enumerate T cells in PB and PLO of NOD mice.  

Results: IGRP specific T cells in the PLO increased as NOD mice aged, and as severity of insulitis increased. To test if this is due to migration of T cells from the islets to the PLO, infiltrated islets grafted into immunodeficient mice caused T1D in the hosts, implying that T cells can migrate from transplanted islets into the PB and reinvade the host islets. IGRP specific T cells from the PLO and PB of diabetic NOD mice are antigen experienced, long-lived memory T cells.

Summary: Long-lived memory autoreactive T cells in PLO or PB correlate with insulitis severity and reflect islet pathology, and could be a useful biomarker.