Functional cytotoxic T lymphocytes against IGRP 206-214 predict diabetes in the non-obese diabetic mouse

CD8 ⁺ T cells are prominent in autoimmune diabetes of both humans and non-obese diabetic (NOD) mice. For example, CD8 ⁺ T cells against islet-specific glucose 6-phosphatase catalytic subunit-related protein (IGRP) can be detected readily in older NOD mice. It has been suggested that the enumeration of islet-specific CD8 ⁺ T cells in the peripheral blood may be a predictive biomarker for autoimmune type 1 diabetes (T1D). Here, we determined the natural history of the functional endogenous IGRP 206-214-specific cytotoxic T lymphocytes (CTLs) in NOD mice with regard to age (3-to 15-week-old pre-diabetic mice and diabetic mice) and sex. We demonstrated that in vivo IGRP 206-214-specific CTLs significantly increased after 12 weeks of age and in vivo cytotoxicity in female NOD mice was significantly higher than in male NOD mice. To determine the in vivo IGRP 206-214-specific CTL frequency without killing the mice, we performed splenectomies on a cohort of mice after injecting IGRP 206-214-coated targets and then followed their diabetes progression. We found that CTL frequency correlated with future of disease onset. Thus, our data support that IGRP 206-214-specific CTLs may be a potent biomarker for T1D.