IFN-gamma production by alloantigen-reactive regulatory T cells is important for their regulatory function in vivo.

The significance of cytokine production by CD4(+) regulatory T (T reg) cells after antigen exposure in vivo and its impact on their regulatory activity remains unclear. Pretreatment with donor alloantigen under the cover of anti-CD4 therapy generates alloantigen reactive T reg cells that can prevent...

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Main Authors: Sawitzki, B, Kingsley, C, Oliveira, V, Karim, M, Herber, M, Wood, K
Format: Journal article
Language:English
Published: 2005
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author Sawitzki, B
Kingsley, C
Oliveira, V
Karim, M
Herber, M
Wood, K
author_facet Sawitzki, B
Kingsley, C
Oliveira, V
Karim, M
Herber, M
Wood, K
author_sort Sawitzki, B
collection OXFORD
description The significance of cytokine production by CD4(+) regulatory T (T reg) cells after antigen exposure in vivo and its impact on their regulatory activity remains unclear. Pretreatment with donor alloantigen under the cover of anti-CD4 therapy generates alloantigen reactive T reg cells that can prevent rejection of donor-specific skin grafts that are mediated by naive CD45RB(high)CD4(+) T cells. To examine the kinetics and importance of cytokine gene transcription by such alloantigen-reactive T reg cells, pretreated mice were rechallenged with donor alloantigen in vivo. CD25(+)CD4(+) T cells, but not CD25(-)CD4(+) T cells, showed a fivefold increase in IFN-gamma mRNA expression within 24 h of re-encountering alloantigen in vivo. This expression kinetic was highly antigen-specific and was of functional significance. Neutralizing IFN-gamma at the time of cotransfer of alloantigen reactive T reg cells, together with CD45RB(high)CD4(+) effector T cells into Rag(-/-) skin graft recipients, resulted in skin graft necrosis in all recipients; the generation and function of alloantigen-reactive T reg cells was impaired dramatically in IFN-gamma-deficient mice. These data support a unique role for IFN-gamma in the functional activity of alloantigen-reactive T reg cells during the development of operational tolerance to donor alloantigens in vivo.
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spelling oxford-uuid:76c4f189-7cbd-4ef6-8e01-0c41cf7d21532022-03-26T20:18:29ZIFN-gamma production by alloantigen-reactive regulatory T cells is important for their regulatory function in vivo.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:76c4f189-7cbd-4ef6-8e01-0c41cf7d2153EnglishSymplectic Elements at Oxford2005Sawitzki, BKingsley, COliveira, VKarim, MHerber, MWood, KThe significance of cytokine production by CD4(+) regulatory T (T reg) cells after antigen exposure in vivo and its impact on their regulatory activity remains unclear. Pretreatment with donor alloantigen under the cover of anti-CD4 therapy generates alloantigen reactive T reg cells that can prevent rejection of donor-specific skin grafts that are mediated by naive CD45RB(high)CD4(+) T cells. To examine the kinetics and importance of cytokine gene transcription by such alloantigen-reactive T reg cells, pretreated mice were rechallenged with donor alloantigen in vivo. CD25(+)CD4(+) T cells, but not CD25(-)CD4(+) T cells, showed a fivefold increase in IFN-gamma mRNA expression within 24 h of re-encountering alloantigen in vivo. This expression kinetic was highly antigen-specific and was of functional significance. Neutralizing IFN-gamma at the time of cotransfer of alloantigen reactive T reg cells, together with CD45RB(high)CD4(+) effector T cells into Rag(-/-) skin graft recipients, resulted in skin graft necrosis in all recipients; the generation and function of alloantigen-reactive T reg cells was impaired dramatically in IFN-gamma-deficient mice. These data support a unique role for IFN-gamma in the functional activity of alloantigen-reactive T reg cells during the development of operational tolerance to donor alloantigens in vivo.
spellingShingle Sawitzki, B
Kingsley, C
Oliveira, V
Karim, M
Herber, M
Wood, K
IFN-gamma production by alloantigen-reactive regulatory T cells is important for their regulatory function in vivo.
title IFN-gamma production by alloantigen-reactive regulatory T cells is important for their regulatory function in vivo.
title_full IFN-gamma production by alloantigen-reactive regulatory T cells is important for their regulatory function in vivo.
title_fullStr IFN-gamma production by alloantigen-reactive regulatory T cells is important for their regulatory function in vivo.
title_full_unstemmed IFN-gamma production by alloantigen-reactive regulatory T cells is important for their regulatory function in vivo.
title_short IFN-gamma production by alloantigen-reactive regulatory T cells is important for their regulatory function in vivo.
title_sort ifn gamma production by alloantigen reactive regulatory t cells is important for their regulatory function in vivo
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