Local induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues.

2.50
Hdl Handle:
http://hdl.handle.net/10033/117075
Title:
Local induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues.
Authors:
Fleissner, Diana; Hansen, Wiebke; Geffers, Robert; Buer, Jan; Westendorf, Astrid M
Abstract:
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.
Affiliation:
Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Citation:
Local induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues. 2010, 5 (10):e15373 PLoS ONE
Journal:
PloS one
Issue Date:
2010
URI:
http://hdl.handle.net/10033/117075
DOI:
10.1371/journal.pone.0015373
PubMed ID:
20975955
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
Publications of Dept. Cell Biology (ZB)

Full metadata record

DC FieldValue Language
dc.contributor.authorFleissner, Dianaen
dc.contributor.authorHansen, Wiebkeen
dc.contributor.authorGeffers, Roberten
dc.contributor.authorBuer, Janen
dc.contributor.authorWestendorf, Astrid Men
dc.date.accessioned2010-12-03T10:43:41Z-
dc.date.available2010-12-03T10:43:41Z-
dc.date.issued2010-
dc.identifier.citationLocal induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues. 2010, 5 (10):e15373 PLoS ONEen
dc.identifier.issn1932-6203-
dc.identifier.pmid20975955-
dc.identifier.doi10.1371/journal.pone.0015373-
dc.identifier.urihttp://hdl.handle.net/10033/117075-
dc.description.abstractBACKGROUND: 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.en
dc.language.isoenen
dc.titleLocal induction of immunosuppressive CD8+ T cells in the gut-associated lymphoid tissues.en
dc.typeArticleen
dc.contributor.departmentInstitute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.en
dc.identifier.journalPloS oneen

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