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Diversity of a diabetegenic T cell population decreases with age in pre‐diabetic NOD mice
Author(s) -
Vincent Benjamin Garrett,
Young Ellen F.,
Stevens Rosemary,
Buntzman Adam S.,
Kepler Thomas B.,
Frelinger Jeffrey A.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.462
Subject(s) - nod mice , spleen , biology , population , cd8 , pancreatic islets , immunology , dominance (genetics) , islet , nod , immune system , diabetes mellitus , autoimmunity , endocrinology , medicine , genetics , environmental health , gene
The non‐obese diabetic (NOD) mouse develops autoimmune‐mediated β‐islet destruction and provides a model for the study of type I diabetes (T1D). We showed that the diversity of a cell population important in diabetegenesis (IGRP‐specific CD8 + T‐cells) is exquisitely low in the pancreatic islets and peripheral blood of 20wk‐old NOD mice. It is important to know whether this restriction occurs in younger mice as well. We used single‐cell RT/PCR and sequencing to determine the diversity of IGRP‐specific CD8 + T cells isolated from various tissues of NOD mice at ages 8–14 weeks. The diversity in the islets was significantly less at 12–14 weeks than it was at 8–10 weeks, a difference that was not seen in the pancreatic lymph nodes (PLNs) or spleen. The decreased diversity was associated with increasing dominance of TRBV 13‐3 and the emergence into dominance of TRJB 1–2. The number of clonotypes shared between different mice increased over time in the islets but not in the PLNs or spleen. Although 14 motifs that spanned the cdr3β region were discovered in the pooled sequences, there were no significant correlations between motif frequency and tissue or age. These data show that the population dynamics of IGRP‐specific CD8 + T cells differ in the islets and periphery; the islet population becomes more homogenous and more public as disease progresses, and this change is marked primarily by shifts in Vβ and Jβ usage.