Autocrine IFNγ controls the regulatory function of lymphoproliferative double negative T cells.
TCRαβ(+) CD4(-)CD8(-)NK(-) double negative T cells (DN T cells) can act as regulatory T cells to inhibit allograft rejection and autoimmunity. Their role in graft-versus-host disease and mechanisms of suppression remain elusive. In this study, we demonstrate that DN T cells can inhibit CD4(+) T cell...
| Main Authors: | , , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado: |
Public Library of Science
2012
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| _version_ | 1826290329564741632 |
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| author | Juvet, S Han, M Vanama, R Joe, B Kim, E Zhao, F Jeon, C Adeyi, O Zhang, L |
| author_facet | Juvet, S Han, M Vanama, R Joe, B Kim, E Zhao, F Jeon, C Adeyi, O Zhang, L |
| author_sort | Juvet, S |
| collection | OXFORD |
| description | TCRαβ(+) CD4(-)CD8(-)NK(-) double negative T cells (DN T cells) can act as regulatory T cells to inhibit allograft rejection and autoimmunity. Their role in graft-versus-host disease and mechanisms of suppression remain elusive. In this study, we demonstrate that DN T cells can inhibit CD4(+) T cell-mediated GVHD in a semi-allogeneic model of bone marrow transplantation. Furthermore, we present evidence of a novel autocrine IFNγ signaling pathway in Fas-deficient C57BL/6.lpr (B6.lpr) DN T cells. B6.lpr DN T cells lacking IFNγ or its receptor were impaired in their ability to suppress syngeneic CD4(+) T cells responding to alloantigen stimulation both in vitro and in vivo. Autocrine IFNγ signaling was required for sustained B6.lpr DN T cell IFNγ secretion in vivo and for upregulation of surface Fas ligand expression during TCR stimulation. Fas ligand (FasL) expression by B6.lpr DN T cells permitted lysis of activated CD4(+) T cells and was required for suppression of GVHD. Collectively, our data indicate that DN T cells can inhibit GVHD and that IFNγ plays a critical autocrine role in controlling the regulatory function of B6.lpr DN T cells. |
| first_indexed | 2024-03-07T02:42:31Z |
| format | Journal article |
| id | oxford-uuid:aaf07c2e-5cf2-48f0-bc67-5620541af486 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:42:31Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:aaf07c2e-5cf2-48f0-bc67-5620541af4862022-03-27T03:18:34ZAutocrine IFNγ controls the regulatory function of lymphoproliferative double negative T cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:aaf07c2e-5cf2-48f0-bc67-5620541af486EnglishSymplectic Elements at OxfordPublic Library of Science2012Juvet, SHan, MVanama, RJoe, BKim, EZhao, FJeon, CAdeyi, OZhang, LTCRαβ(+) CD4(-)CD8(-)NK(-) double negative T cells (DN T cells) can act as regulatory T cells to inhibit allograft rejection and autoimmunity. Their role in graft-versus-host disease and mechanisms of suppression remain elusive. In this study, we demonstrate that DN T cells can inhibit CD4(+) T cell-mediated GVHD in a semi-allogeneic model of bone marrow transplantation. Furthermore, we present evidence of a novel autocrine IFNγ signaling pathway in Fas-deficient C57BL/6.lpr (B6.lpr) DN T cells. B6.lpr DN T cells lacking IFNγ or its receptor were impaired in their ability to suppress syngeneic CD4(+) T cells responding to alloantigen stimulation both in vitro and in vivo. Autocrine IFNγ signaling was required for sustained B6.lpr DN T cell IFNγ secretion in vivo and for upregulation of surface Fas ligand expression during TCR stimulation. Fas ligand (FasL) expression by B6.lpr DN T cells permitted lysis of activated CD4(+) T cells and was required for suppression of GVHD. Collectively, our data indicate that DN T cells can inhibit GVHD and that IFNγ plays a critical autocrine role in controlling the regulatory function of B6.lpr DN T cells. |
| spellingShingle | Juvet, S Han, M Vanama, R Joe, B Kim, E Zhao, F Jeon, C Adeyi, O Zhang, L Autocrine IFNγ controls the regulatory function of lymphoproliferative double negative T cells. |
| title | Autocrine IFNγ controls the regulatory function of lymphoproliferative double negative T cells. |
| title_full | Autocrine IFNγ controls the regulatory function of lymphoproliferative double negative T cells. |
| title_fullStr | Autocrine IFNγ controls the regulatory function of lymphoproliferative double negative T cells. |
| title_full_unstemmed | Autocrine IFNγ controls the regulatory function of lymphoproliferative double negative T cells. |
| title_short | Autocrine IFNγ controls the regulatory function of lymphoproliferative double negative T cells. |
| title_sort | autocrine ifnγ controls the regulatory function of lymphoproliferative double negative t cells |
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