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...
Main Authors: | , , , , , |
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Format: | Journal article |
Language: | English |
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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. |
first_indexed | 2024-03-07T00:03:30Z |
format | Journal article |
id | oxford-uuid:76c4f189-7cbd-4ef6-8e01-0c41cf7d2153 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T00:03:30Z |
publishDate | 2005 |
record_format | dspace |
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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