TY - JOUR
T1 - Effector-memory T cells develop in islets and report islet pathology in type 1 diabetes
AU - Chee, Jonathan
AU - Ko, Hyun Ja
AU - Skowera, Ania
AU - Jhala, Gaurang
AU - Catterall, Tara
AU - Graham, Kate L.
AU - Sutherland, Robyn M.
AU - Thomas, Helen E.
AU - Lew, Andrew M.
AU - Peakman, Mark
AU - Kay, Thomas W.H.
AU - Krishnamurthy, Balasubramanian
PY - 2014/1/15
Y1 - 2014/1/15
N2 - CD8+ T cells are critical in human type 1 diabetes and in the NOD mouse. In this study, we elucidated the natural history of isletspecific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific CD8 + T cells in NOD diabetes using MHCtetramer technology. IGRP 206-214-specific T cells in the peripheral lymphoid tissue increased with age, and their numbers correlated with insulitis progression. IGRP 206-214-specific T cells in the peripheral lymphoid tissue expressed markers of chronic Ag stimulation, and their numbers were stable after diagnosis of diabetes, consistent with their memory phenotype. IGRP206-214- specific T cells in NOD mice expand, acquire the phenotype of effector-memory T cells in the islets, and emigrate to the peripheral lymphoid tissue. Our observations suggest that enumeration of effector-memory T cells of multiple autoantigen specificities in the periphery of type 1 diabetic subjects could be a reliable reporter for progression of islet pathology.
AB - CD8+ T cells are critical in human type 1 diabetes and in the NOD mouse. In this study, we elucidated the natural history of isletspecific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific CD8 + T cells in NOD diabetes using MHCtetramer technology. IGRP 206-214-specific T cells in the peripheral lymphoid tissue increased with age, and their numbers correlated with insulitis progression. IGRP 206-214-specific T cells in the peripheral lymphoid tissue expressed markers of chronic Ag stimulation, and their numbers were stable after diagnosis of diabetes, consistent with their memory phenotype. IGRP206-214- specific T cells in NOD mice expand, acquire the phenotype of effector-memory T cells in the islets, and emigrate to the peripheral lymphoid tissue. Our observations suggest that enumeration of effector-memory T cells of multiple autoantigen specificities in the periphery of type 1 diabetic subjects could be a reliable reporter for progression of islet pathology.
UR - http://www.scopus.com/inward/record.url?scp=84892686874&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1302100
DO - 10.4049/jimmunol.1302100
M3 - Article
C2 - 24337380
AN - SCOPUS:84892686874
SN - 0022-1767
VL - 192
SP - 572
EP - 580
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -
