Intra-islet proliferation of cytotoxic T lymphocytes contributes to insulitis progression

European Journal of Immunology
Kate L GrahamThomas W H Kay

Abstract

Infiltration of pancreatic islets by immune cells, termed insulitis, increases progressively once it begins and leads to clinical type 1 diabetes. But even after diagnosis some islets remain unaffected and infiltration is patchy rather than uniform. Traffic of autoreactive T cells into the pancreas is likely to contribute to insulitis progression but it could also depend on T-cell proliferation within islets. This study utilizes transgenic NOD mice to assess the relative contributions of these two mechanisms. Progression of insulitis in NOD8.3 TCR transgenic mice was mildly reduced by inhibition of T-cell migration with the drug FTY720. In FTY720-treated mice, reduced beta cell MHC class I expression prevented progression of insulitis both within affected islets and to previously unaffected islets. CTL proliferation was significantly reduced in islets with reduced or absent beta cell expression of MHC class I protein. This indicates that intra-islet proliferation, apparently dependent on beta cell antigen presentation, in addition to recruitment, is a significant factor in progression of insulitis.

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Citations

Aug 8, 2013·Current Diabetes Reports·Philip J O'ConnellAndrew M Lew
Jan 1, 2012·The Review of Diabetic Studies : RDS·Kate L GrahamThomas W H Kay
Jan 20, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Naresh SachdevaSanjay Kumar Bhadada
Sep 30, 2016·Clinical Reviews in Allergy & Immunology·Ayelet KaminitzNadir Askenasy
Mar 7, 2017·Scientific Reports·Han-Huei LinShey-Cherng Tzou
Apr 13, 2017·Nature Communications·Robyn M SutherlandAndrew M Lew
Apr 2, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Matthew H ForsbergYi-Guang Chen
Feb 28, 2018·Endocrine Connections·Darling M Rojas-CanalesPatrick T Coates
Dec 17, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robin S LindsayRachel S Friedman
Sep 30, 2017·Frontiers in Endocrinology·Brittney N Newby, Clayton E Mathews
Jan 14, 2017·Frontiers in Physiology·Kyle C A WedgwoodKrasimira Tsaneva-Atanasova
Mar 25, 2018·Science Immunology·Gustaf ChristofferssonMatthias G von Herrath
Sep 12, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ashley E CieckoYi-Guang Chen

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