Effector and naturally occurring regulatory T cells display no abnormalities in activation induced cell death in NOD mice.

BACKGROUND: Disturbed peripheral negative regulation might contribute to evolution of autoimmune insulitis in type 1 diabetes. This study evaluates the sensitivity of naïve/effector (Teff) and regulatory T cells (Treg) to activation-induced cell death mediated by Fas cross-linking in NOD and wild-ty...

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Main Authors: Ayelet Kaminitz, Esma S Yolcu, Enosh M Askenasy, Jerry Stein, Isaac Yaniv, Haval Shirwan, Nadir Askenasy
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3124542?pdf=render
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author Ayelet Kaminitz
Esma S Yolcu
Enosh M Askenasy
Jerry Stein
Isaac Yaniv
Haval Shirwan
Nadir Askenasy
author_facet Ayelet Kaminitz
Esma S Yolcu
Enosh M Askenasy
Jerry Stein
Isaac Yaniv
Haval Shirwan
Nadir Askenasy
author_sort Ayelet Kaminitz
collection DOAJ
description BACKGROUND: Disturbed peripheral negative regulation might contribute to evolution of autoimmune insulitis in type 1 diabetes. This study evaluates the sensitivity of naïve/effector (Teff) and regulatory T cells (Treg) to activation-induced cell death mediated by Fas cross-linking in NOD and wild-type mice. PRINCIPAL FINDINGS: Both effector (CD25(-), FoxP3(-)) and suppressor (CD25(+), FoxP3(+)) CD4(+) T cells are negatively regulated by Fas cross-linking in mixed splenocyte populations of NOD, wild type mice and FoxP3-GFP trangeneess. Proliferation rates and sensitivity to Fas cross-linking are dissociated in Treg cells: fast cycling induced by IL-2 and CD3/CD28 stimulation improve Treg resistance to Fas-ligand (FasL) in both strains. The effector and suppressor CD4(+) subsets display balanced sensitivity to negative regulation under baseline conditions, IL-2 and CD3/CD28 stimulation, indicating that stimulation does not perturb immune homeostasis in NOD mice. Effective autocrine apoptosis of diabetogenic cells was evident from delayed onset and reduced incidence of adoptive disease transfer into NOD.SCID by CD4(+)CD25(-) T cells decorated with FasL protein. Treg resistant to Fas-mediated apoptosis retain suppressive activity in vitro. The only detectable differential response was reduced Teff proliferation and upregulation of CD25 following CD3-activation in NOD mice. CONCLUSION: These data document negative regulation of effector and suppressor cells by Fas cross-linking and dissociation between sensitivity to apoptosis and proliferation in stimulated Treg. There is no evidence that perturbed AICD in NOD mice initiates or promotes autoimmune insulitis.
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spelling doaj.art-550adadd10774031a12a319ee3e25e7d2022-12-21T19:25:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0166e2163010.1371/journal.pone.0021630Effector and naturally occurring regulatory T cells display no abnormalities in activation induced cell death in NOD mice.Ayelet KaminitzEsma S YolcuEnosh M AskenasyJerry SteinIsaac YanivHaval ShirwanNadir AskenasyBACKGROUND: Disturbed peripheral negative regulation might contribute to evolution of autoimmune insulitis in type 1 diabetes. This study evaluates the sensitivity of naïve/effector (Teff) and regulatory T cells (Treg) to activation-induced cell death mediated by Fas cross-linking in NOD and wild-type mice. PRINCIPAL FINDINGS: Both effector (CD25(-), FoxP3(-)) and suppressor (CD25(+), FoxP3(+)) CD4(+) T cells are negatively regulated by Fas cross-linking in mixed splenocyte populations of NOD, wild type mice and FoxP3-GFP trangeneess. Proliferation rates and sensitivity to Fas cross-linking are dissociated in Treg cells: fast cycling induced by IL-2 and CD3/CD28 stimulation improve Treg resistance to Fas-ligand (FasL) in both strains. The effector and suppressor CD4(+) subsets display balanced sensitivity to negative regulation under baseline conditions, IL-2 and CD3/CD28 stimulation, indicating that stimulation does not perturb immune homeostasis in NOD mice. Effective autocrine apoptosis of diabetogenic cells was evident from delayed onset and reduced incidence of adoptive disease transfer into NOD.SCID by CD4(+)CD25(-) T cells decorated with FasL protein. Treg resistant to Fas-mediated apoptosis retain suppressive activity in vitro. The only detectable differential response was reduced Teff proliferation and upregulation of CD25 following CD3-activation in NOD mice. CONCLUSION: These data document negative regulation of effector and suppressor cells by Fas cross-linking and dissociation between sensitivity to apoptosis and proliferation in stimulated Treg. There is no evidence that perturbed AICD in NOD mice initiates or promotes autoimmune insulitis.http://europepmc.org/articles/PMC3124542?pdf=render
spellingShingle Ayelet Kaminitz
Esma S Yolcu
Enosh M Askenasy
Jerry Stein
Isaac Yaniv
Haval Shirwan
Nadir Askenasy
Effector and naturally occurring regulatory T cells display no abnormalities in activation induced cell death in NOD mice.
PLoS ONE
title Effector and naturally occurring regulatory T cells display no abnormalities in activation induced cell death in NOD mice.
title_full Effector and naturally occurring regulatory T cells display no abnormalities in activation induced cell death in NOD mice.
title_fullStr Effector and naturally occurring regulatory T cells display no abnormalities in activation induced cell death in NOD mice.
title_full_unstemmed Effector and naturally occurring regulatory T cells display no abnormalities in activation induced cell death in NOD mice.
title_short Effector and naturally occurring regulatory T cells display no abnormalities in activation induced cell death in NOD mice.
title_sort effector and naturally occurring regulatory t cells display no abnormalities in activation induced cell death in nod mice
url http://europepmc.org/articles/PMC3124542?pdf=render
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