Local induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues.
BACKGROUND: In contrast to intestinal CD4(+) regulatory T cells (T(regs)), the generation and function of immunomodulatory intestinal CD8(+) T cells is less well defined. To dissect the immunologic mechanisms of CD8(+) T cell function in the mucosa, reactivity against hemagglutinin (HA) expressed in...
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doaj-119c584f57ef45138461e048d7b1df0d2020-11-25T01:46:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-01510e1537310.1371/journal.pone.0015373Local induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues.Diana FleissnerWiebke HansenRobert GeffersJan BuerAstrid M WestendorfBACKGROUND: In contrast to intestinal CD4(+) regulatory T cells (T(regs)), the generation and function of immunomodulatory intestinal CD8(+) T cells is less well defined. To dissect the immunologic mechanisms of CD8(+) T cell function in the mucosa, reactivity against hemagglutinin (HA) expressed in intestinal epithelial cells of mice bearing a MHC class-I-restricted T-cell-receptor specific for HA was studied. METHODOLOGY AND PRINCIPAL FINDINGS: HA-specific CD8(+) T cells were isolated from gut-associated tissues and phenotypically and functionally characterized for the expression of Foxp3(+) and their suppressive capacity. We demonstrate that intestinal HA expression led to peripheral induction of HA-specific CD8(+)Foxp3(+) T cells. Antigen-experienced CD8(+) T cells in this transgenic mouse model suppressed the proliferation of CD8(+) and CD4(+) T cells in vitro. Gene expression analysis of suppressive HA-specific CD8(+) T cells revealed a specific up-regulation of CD103, Nrp1, Tnfrsf9 and Pdcd1, molecules also expressed on CD4(+) T(reg) subsets. Finally, gut-associated dendritic cells were able to induce HA-specific CD8(+)Foxp3(+) T cells. CONCLUSION AND SIGNIFICANCE: We demonstrate that gut specific antigen presentation is sufficient to induce CD8(+) T(regs)in vivo which may maintain intestinal homeostasis by down-modulating effector functions of T cells.http://europepmc.org/articles/PMC2958146?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Diana Fleissner Wiebke Hansen Robert Geffers Jan Buer Astrid M Westendorf |
spellingShingle |
Diana Fleissner Wiebke Hansen Robert Geffers Jan Buer Astrid M Westendorf Local induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues. PLoS ONE |
author_facet |
Diana Fleissner Wiebke Hansen Robert Geffers Jan Buer Astrid M Westendorf |
author_sort |
Diana Fleissner |
title |
Local induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues. |
title_short |
Local induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues. |
title_full |
Local induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues. |
title_fullStr |
Local induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues. |
title_full_unstemmed |
Local induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues. |
title_sort |
local induction of immunosuppressive cd8+ t cells in the gut-associated lymphoid tissues. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2010-01-01 |
description |
BACKGROUND: In contrast to intestinal CD4(+) regulatory T cells (T(regs)), the generation and function of immunomodulatory intestinal CD8(+) T cells is less well defined. To dissect the immunologic mechanisms of CD8(+) T cell function in the mucosa, reactivity against hemagglutinin (HA) expressed in intestinal epithelial cells of mice bearing a MHC class-I-restricted T-cell-receptor specific for HA was studied. METHODOLOGY AND PRINCIPAL FINDINGS: HA-specific CD8(+) T cells were isolated from gut-associated tissues and phenotypically and functionally characterized for the expression of Foxp3(+) and their suppressive capacity. We demonstrate that intestinal HA expression led to peripheral induction of HA-specific CD8(+)Foxp3(+) T cells. Antigen-experienced CD8(+) T cells in this transgenic mouse model suppressed the proliferation of CD8(+) and CD4(+) T cells in vitro. Gene expression analysis of suppressive HA-specific CD8(+) T cells revealed a specific up-regulation of CD103, Nrp1, Tnfrsf9 and Pdcd1, molecules also expressed on CD4(+) T(reg) subsets. Finally, gut-associated dendritic cells were able to induce HA-specific CD8(+)Foxp3(+) T cells. CONCLUSION AND SIGNIFICANCE: We demonstrate that gut specific antigen presentation is sufficient to induce CD8(+) T(regs)in vivo which may maintain intestinal homeostasis by down-modulating effector functions of T cells. |
url |
http://europepmc.org/articles/PMC2958146?pdf=render |
work_keys_str_mv |
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