Regulatory T cells in γ irradiation-induced immune suppression.
Sublethal total body γ irradiation (TBI) of mammals causes generalized immunosuppression, in part by induction of lymphocyte apoptosis. Here, we provide evidence that a part of this immune suppression may be attributable to dysfunction of immune regulation. We investigated the effects of sublethal T...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2012-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3378522?pdf=render |
id |
doaj-ef60ffa8fc60449ba38f709be6ba4864 |
---|---|
record_format |
Article |
spelling |
doaj-ef60ffa8fc60449ba38f709be6ba48642020-11-25T01:13:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3909210.1371/journal.pone.0039092Regulatory T cells in γ irradiation-induced immune suppression.Hugh I McFarlandMontserrat PuigLucja T GrajkowskaKazuhide TsujiJay P LeeKaren P MasonDaniela VerthelyiAmy S RosenbergSublethal total body γ irradiation (TBI) of mammals causes generalized immunosuppression, in part by induction of lymphocyte apoptosis. Here, we provide evidence that a part of this immune suppression may be attributable to dysfunction of immune regulation. We investigated the effects of sublethal TBI on T cell memory responses to gain insight into the potential for loss of vaccine immunity following such exposure. We show that in mice primed to an MHC class I alloantigen, the accelerated graft rejection T memory response is specifically lost several weeks following TBI, whereas identically treated naïve mice at the same time point had completely recovered normal rejection kinetics. Depletion in vivo with anti-CD4 or anti-CD25 showed that the mechanism involved cells consistent with a regulatory T cell (T reg) phenotype. The loss of the T memory response following TBI was associated with a relative increase of CD4+CD25+ Foxp3+ expressing T regs, as compared to the CD8+ T effector cells requisite for skin graft rejection. The radiation-induced T memory suppression was shown to be antigen-specific in that a third party ipsilateral graft rejected with normal kinetics. Remarkably, following the eventual rejection of the first MHC class I disparate skin graft, the suppressive environment was maintained, with markedly prolonged survival of a second identical allograft. These findings have potential importance as regards the immunologic status of T memory responses in victims of ionizing radiation exposure and apoptosis-inducing therapies.http://europepmc.org/articles/PMC3378522?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hugh I McFarland Montserrat Puig Lucja T Grajkowska Kazuhide Tsuji Jay P Lee Karen P Mason Daniela Verthelyi Amy S Rosenberg |
spellingShingle |
Hugh I McFarland Montserrat Puig Lucja T Grajkowska Kazuhide Tsuji Jay P Lee Karen P Mason Daniela Verthelyi Amy S Rosenberg Regulatory T cells in γ irradiation-induced immune suppression. PLoS ONE |
author_facet |
Hugh I McFarland Montserrat Puig Lucja T Grajkowska Kazuhide Tsuji Jay P Lee Karen P Mason Daniela Verthelyi Amy S Rosenberg |
author_sort |
Hugh I McFarland |
title |
Regulatory T cells in γ irradiation-induced immune suppression. |
title_short |
Regulatory T cells in γ irradiation-induced immune suppression. |
title_full |
Regulatory T cells in γ irradiation-induced immune suppression. |
title_fullStr |
Regulatory T cells in γ irradiation-induced immune suppression. |
title_full_unstemmed |
Regulatory T cells in γ irradiation-induced immune suppression. |
title_sort |
regulatory t cells in γ irradiation-induced immune suppression. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
Sublethal total body γ irradiation (TBI) of mammals causes generalized immunosuppression, in part by induction of lymphocyte apoptosis. Here, we provide evidence that a part of this immune suppression may be attributable to dysfunction of immune regulation. We investigated the effects of sublethal TBI on T cell memory responses to gain insight into the potential for loss of vaccine immunity following such exposure. We show that in mice primed to an MHC class I alloantigen, the accelerated graft rejection T memory response is specifically lost several weeks following TBI, whereas identically treated naïve mice at the same time point had completely recovered normal rejection kinetics. Depletion in vivo with anti-CD4 or anti-CD25 showed that the mechanism involved cells consistent with a regulatory T cell (T reg) phenotype. The loss of the T memory response following TBI was associated with a relative increase of CD4+CD25+ Foxp3+ expressing T regs, as compared to the CD8+ T effector cells requisite for skin graft rejection. The radiation-induced T memory suppression was shown to be antigen-specific in that a third party ipsilateral graft rejected with normal kinetics. Remarkably, following the eventual rejection of the first MHC class I disparate skin graft, the suppressive environment was maintained, with markedly prolonged survival of a second identical allograft. These findings have potential importance as regards the immunologic status of T memory responses in victims of ionizing radiation exposure and apoptosis-inducing therapies. |
url |
http://europepmc.org/articles/PMC3378522?pdf=render |
work_keys_str_mv |
AT hughimcfarland regulatorytcellsingirradiationinducedimmunesuppression AT montserratpuig regulatorytcellsingirradiationinducedimmunesuppression AT lucjatgrajkowska regulatorytcellsingirradiationinducedimmunesuppression AT kazuhidetsuji regulatorytcellsingirradiationinducedimmunesuppression AT jayplee regulatorytcellsingirradiationinducedimmunesuppression AT karenpmason regulatorytcellsingirradiationinducedimmunesuppression AT danielaverthelyi regulatorytcellsingirradiationinducedimmunesuppression AT amysrosenberg regulatorytcellsingirradiationinducedimmunesuppression |
_version_ |
1725161276935503872 |