Interaction between Treg apoptosis pathways, Treg function and HLA risk evolves during type 1 diabetes pathogenesis.

PloS One
S Glisic, P Jailwala

Abstract

We have previously reported increased apoptosis of regulatory T cells (Tregs) in recent-onset Type 1 Diabetes subjects (RO T1D) in the honeymoon phase and in multiple autoantibody-positive (Ab+) subjects, some of which are developing T1D. We have also reported that increased Treg apoptosis was associated with High HLA risk and that it subsided with cessation of honeymoon period. In this report, we present results generated using genetics, genomics, functional cell-based assays and flow cytometry to assess cellular changes at the T-cell level during T1D pathogenesis. We measured ex vivo Treg apoptosis and Treg function, surface markers expression, expression of HLA class II genes, the influence of HLA risk on Treg apoptosis and function, and evaluated contribution of genes reported to be involved in the apoptosis process. This integrated comprehensive approach uncovered important information that can serve as a basis for future studies aimed to modulate Treg cell responsiveness to apoptotic signals in autoimmunity. For example, T1D will progress in those subjects where increased Treg apoptosis is accompanied with decreased Treg function. Furthermore, Tregs from High HLA risk healthy controls had increased Treg apoptosis levels a...Continue Reading

References

Jun 28, 1990·The New England Journal of Medicine·J M BaischJ D Capra
Sep 1, 1987·Human Immunology·L ShooksterR Winchester
Oct 12, 1974·Lancet·J NerupA Svejgaard
Dec 1, 1984·Clinical Genetics·J I Rotter, E M Landaw
Jan 1, 1994·European Journal of Immunology·V BarnabaA Lanzavecchia
Mar 1, 1996·The Journal of Experimental Medicine·W W KwokD M Koelle
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·J XiangS J Korsmeyer
Jan 1, 1997·Immunogenetics·E Morzycka-WroblewskaM F Kagnoff
Mar 6, 1999·Cellular Immunology·A ThibeaultR Al-Daccak
Feb 13, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·T J YunE A Clark
Mar 10, 2001·Recent Progress in Hormone Research·M J RedondoG S Eisenbarth
Jan 5, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tjadine M HollingPeter J van den Elsen
Mar 1, 2002·Journal of Autoimmunity·Carla J GreenbaumJanelle A Noble
Jul 18, 2002·European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics·H DonnerK Badenhoop
Jul 26, 2002·Genes and Immunity·F Pociot, M F McDermott
Nov 1, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·James W RussellEva L Feldman
May 31, 2003·The Journal of Biological Chemistry·Christian StehlikJohn C Reed
Aug 22, 2003·Clinical and Experimental Immunology·W ReinischM Willheim
Jun 17, 2004·Molecular and Cellular Biology·Han-Ming ShenZheng-gang Liu
Jun 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Benedikt FritzschingElisabeth Suri-Payer
Feb 24, 2006·American Journal of Physiology. Endocrinology and Metabolism·Yuren WeiMichael J Pagliassotti
Feb 24, 2006·Molecular Biology of the Cell·Christine BonzonDonald D Newmeyer
Apr 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Clare Baecher-AllanDavid A Hafler
Jul 19, 2006·Canadian Journal of Physiology and Pharmacology·Lindsie A RobertsonGeoff H Werstuck

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Methods Mentioned

BETA
FACS
PCR
Fluorescent Activated Cell Sorting

Software Mentioned

Bioconductor
Oligo
Affymetrix
SDS
affyQCreport

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