Title: Functional cytotoxic T lymphocytes against IGRP(206-214) predict diabetes in the non-obese diabetic mouse
Authors: Ko, HJ
Chee, J
Sutherland, RM
Thomas, HE
Zhan, YF
Krishnamurthy, B
Kay, TWH
Lew, AM
Issue Year: 2014
Series IMMUNOLOGY AND CELL BIOLOGY: 92(7): 640-644
Abstract 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 prediabetic 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.
URI: https://publications.svi.edu.au/publications/1800
Other Identifiers 10.1038/icb.2014.29
Publication type Article
Grant ID GNT1037321; GNT1042735;