Peptide specific amelioration of T cell mediated pathogenesis in murine type 1 diabetes

Clinical Immunology : the Official Journal of the Clinical Immunology Society
Valeria JudkowskiDarcy B Wilson

Abstract

NOD mice spontaneously develop insulitis and type 1 diabetes (T1D) mellitus similar to humans. Insulitis without overt disease occurs in the BDC2.5 TCR-transgenic NOD mice that express the rearranged TCR alpha- and beta-chain genes of a diabetogenic T cell clone reactive to an unknown beta cell autoantigen. A previous study identified an extensive panel of peptides that are highly active in stimulating T cells from transgenic BDC2.5 mice in culture. However, none of these peptides cause active disease in NOD and BDC2.5 animals or in NOD recipients of adoptively transferred BDC2.5 T cells following direct immunization in vivo. We show that direct immunization of transgenic BDC2.5 mice causes many BDC2.5 T cells to become activated and apoptotic. Strikingly, soluble peptides administered to recipients of activated, highly pathogenic BDC2.5 T cells results in protection from disease. These results suggest that high affinity peptide analogues of autoimmune epitopes might be useful as therapeutic modulators in active autoimmune disease.

Citations

Feb 8, 2014·Diabetes Management·Dan XuStephen D Miller
Dec 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Stephan KontosJeffrey A Hubbell
Dec 1, 2012·Diabetes, Obesity & Metabolism·D A SchneiderM G von Herrath
Aug 16, 2016·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Fabiola PuentesOlaf Rötzschke
Aug 11, 2007·Nature Reviews. Immunology·Stephen D MillerJoseph R Podojil
Jan 29, 2008·Qualitative Health Research·Vibeke ZoffmannMarit Kirkevold
May 22, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Braxton L JamisonKathryn Haskins
May 4, 2017·Immunological Reviews·Lixin ZhengMichael Lenardo
Aug 10, 2017·Current Diabetes Reports·Tobias Neef, Stephen D Miller
Jun 9, 2021·Current Opinion in Endocrinology, Diabetes, and Obesity·Tobias Neef, Stephen D Miller
Jul 2, 2019·ACS Chemical Biology·Martin A LeonCory Berkland

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