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A clonal model for human CD8+ regulatory T cells: Unrestricted contact‐dependent killing of activated CD4+ T cells

Previous studies in murine systems have demonstrated that CD8 Treg cells down‐regulate immune responses in vivo through suppressing activated CD4 T cells. Here we describe novel regulatory CD8 T‐cell clones isolated from healthy human peripheral blood following in vitro stimulation with autologous E... Full description

Journal Title: European Journal of Immunology January 2012, Vol.42(1), pp.69-79
Main Author: Hu, Dan
Other Authors: Liu, Xia , Zeng, Wanyong , Weiner, Howard L. , Ritz, Jerome
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0014-2980 ; E-ISSN: 1521-4141 ; DOI: 10.1002/eji.201141618
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recordid: wj10.1002/eji.201141618
title: A clonal model for human CD8+ regulatory T cells: Unrestricted contact‐dependent killing of activated CD4+ T cells
format: Article
creator:
  • Hu, Dan
  • Liu, Xia
  • Zeng, Wanyong
  • Weiner, Howard L.
  • Ritz, Jerome
subjects:
  • Cd8 + Treg Cells
  • Suppression And Cytotoxicity
ispartof: European Journal of Immunology, January 2012, Vol.42(1), pp.69-79
description: Previous studies in murine systems have demonstrated that CD8 Treg cells down‐regulate immune responses in vivo through suppressing activated CD4 T cells. Here we describe novel regulatory CD8 T‐cell clones isolated from healthy human peripheral blood following in vitro stimulation with autologous Epstein–Barr virus (EBV)‐specific CD4 T cells. TCR activation of CD4 target T cells was required for CD8 Treg cells to exert suppressive activity, which was mediated through lysis of CD4 targets in a cell contact‐dependent manner. Suppression was independent of Foxp3 expression in CD8 Treg cells, HLA compatibility between CD8 Treg cells and CD4 target cells and antigen‐specificity of CD4 target T cells. CD8 Treg clones expressed CD3 and a variety of TCR V chains as well as CD56, CD69, CD62L and CD95 but did not express CD16, CD161, CXCR4 and CCR7. When used together, antibodies specific for CD11a/CD18 and CD8 inhibited suppressive activity of CD8 Treg clones. The ability to establish clonal CD8 T cells that maintain regulatory function in vitro will facilitate further studies to define this population in vivo and to identify the mechanisms used for recognition and suppression of activated target cells.
language: eng
source:
identifier: ISSN: 0014-2980 ; E-ISSN: 1521-4141 ; DOI: 10.1002/eji.201141618
fulltext: fulltext
issn:
  • 0014-2980
  • 00142980
  • 1521-4141
  • 15214141
url: Link


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titleA clonal model for human CD8+ regulatory T cells: Unrestricted contact‐dependent killing of activated CD4+ T cells
creatorHu, Dan ; Liu, Xia ; Zeng, Wanyong ; Weiner, Howard L. ; Ritz, Jerome
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subjectCd8 + Treg Cells ; Suppression And Cytotoxicity
descriptionPrevious studies in murine systems have demonstrated that CD8 Treg cells down‐regulate immune responses in vivo through suppressing activated CD4 T cells. Here we describe novel regulatory CD8 T‐cell clones isolated from healthy human peripheral blood following in vitro stimulation with autologous Epstein–Barr virus (EBV)‐specific CD4 T cells. TCR activation of CD4 target T cells was required for CD8 Treg cells to exert suppressive activity, which was mediated through lysis of CD4 targets in a cell contact‐dependent manner. Suppression was independent of Foxp3 expression in CD8 Treg cells, HLA compatibility between CD8 Treg cells and CD4 target cells and antigen‐specificity of CD4 target T cells. CD8 Treg clones expressed CD3 and a variety of TCR V chains as well as CD56, CD69, CD62L and CD95 but did not express CD16, CD161, CXCR4 and CCR7. When used together, antibodies specific for CD11a/CD18 and CD8 inhibited suppressive activity of CD8 Treg clones. The ability to establish clonal CD8 T cells that maintain regulatory function in vitro will facilitate further studies to define this population in vivo and to identify the mechanisms used for recognition and suppression of activated target cells.
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descriptionPrevious studies in murine systems have demonstrated that CD8 Treg cells down‐regulate immune responses in vivo through suppressing activated CD4 T cells. Here we describe novel regulatory CD8 T‐cell clones isolated from healthy human peripheral blood following in vitro stimulation with autologous Epstein–Barr virus (EBV)‐specific CD4 T cells. TCR activation of CD4 target T cells was required for CD8 Treg cells to exert suppressive activity, which was mediated through lysis of CD4 targets in a cell contact‐dependent manner. Suppression was independent of Foxp3 expression in CD8 Treg cells, HLA compatibility between CD8 Treg cells and CD4 target cells and antigen‐specificity of CD4 target T cells. CD8 Treg clones expressed CD3 and a variety of TCR V chains as well as CD56, CD69, CD62L and CD95 but did not express CD16, CD161, CXCR4 and CCR7. When used together, antibodies specific for CD11a/CD18 and CD8 inhibited suppressive activity of CD8 Treg clones. The ability to establish clonal CD8 T cells that maintain regulatory function in vitro will facilitate further studies to define this population in vivo and to identify the mechanisms used for recognition and suppression of activated target cells.
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abstractPrevious studies in murine systems have demonstrated that CD8 Treg cells down‐regulate immune responses in vivo through suppressing activated CD4 T cells. Here we describe novel regulatory CD8 T‐cell clones isolated from healthy human peripheral blood following in vitro stimulation with autologous Epstein–Barr virus (EBV)‐specific CD4 T cells. TCR activation of CD4 target T cells was required for CD8 Treg cells to exert suppressive activity, which was mediated through lysis of CD4 targets in a cell contact‐dependent manner. Suppression was independent of Foxp3 expression in CD8 Treg cells, HLA compatibility between CD8 Treg cells and CD4 target cells and antigen‐specificity of CD4 target T cells. CD8 Treg clones expressed CD3 and a variety of TCR V chains as well as CD56, CD69, CD62L and CD95 but did not express CD16, CD161, CXCR4 and CCR7. When used together, antibodies specific for CD11a/CD18 and CD8 inhibited suppressive activity of CD8 Treg clones. The ability to establish clonal CD8 T cells that maintain regulatory function in vitro will facilitate further studies to define this population in vivo and to identify the mechanisms used for recognition and suppression of activated target cells.
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doi10.1002/eji.201141618
pages69-79
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