Identification and expansion of highly suppressive CD8(+)FoxP3(+) regulatory T cells after experimental allogeneic bone marrow transplantation.
FoxP3(+) confers suppressive properties and is confined to regulatory T cells (T(reg)) that potently inhibit autoreactive immune responses. In the transplant setting, natural CD4(+) T(reg) are critical in controlling alloreactivity and the establishment of tolerance. We now identify an important CD8...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2012
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| _version_ | 1826257196811288576 |
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| author | Robb, R Lineburg, K Kuns, R Wilson, Y Raffelt, N Olver, S Varelias, A Alexander, K Teal, B Sparwasser, T Hammerling, G Markey, K Koyama, M Clouston, A Engwerda, C Hill, G MacDonald, K |
| author_facet | Robb, R Lineburg, K Kuns, R Wilson, Y Raffelt, N Olver, S Varelias, A Alexander, K Teal, B Sparwasser, T Hammerling, G Markey, K Koyama, M Clouston, A Engwerda, C Hill, G MacDonald, K |
| author_sort | Robb, R |
| collection | OXFORD |
| description | FoxP3(+) confers suppressive properties and is confined to regulatory T cells (T(reg)) that potently inhibit autoreactive immune responses. In the transplant setting, natural CD4(+) T(reg) are critical in controlling alloreactivity and the establishment of tolerance. We now identify an important CD8(+) population of FoxP3(+) T(reg) that convert from CD8(+) conventional donor T cells after allogeneic but not syngeneic bone marrow transplantation. These CD8(+) T(reg) undergo conversion in the mesenteric lymph nodes under the influence of recipient dendritic cells and TGF-β. Importantly, this population is as important for protection from GVHD as the well-studied natural CD4(+)FoxP3(+) population and is more potent in exerting class I-restricted and antigen-specific suppression in vitro and in vivo. Critically, CD8(+)FoxP3(+) T(reg) are exquisitely sensitive to inhibition by cyclosporine but can be massively and specifically expanded in vivo to prevent GVHD by coadministering rapamycin and IL-2 antibody complexes. CD8(+)FoxP3(+) T(reg) thus represent a new regulatory population with considerable potential to preferentially subvert MHC class I-restricted T-cell responses after bone marrow transplantation. |
| first_indexed | 2024-03-06T18:14:18Z |
| format | Journal article |
| id | oxford-uuid:0416c857-b2f1-450c-9c82-67771223e131 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:14:18Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:0416c857-b2f1-450c-9c82-67771223e1312022-03-26T08:49:56ZIdentification and expansion of highly suppressive CD8(+)FoxP3(+) regulatory T cells after experimental allogeneic bone marrow transplantation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0416c857-b2f1-450c-9c82-67771223e131EnglishSymplectic Elements at Oxford2012Robb, RLineburg, KKuns, RWilson, YRaffelt, NOlver, SVarelias, AAlexander, KTeal, BSparwasser, THammerling, GMarkey, KKoyama, MClouston, AEngwerda, CHill, GMacDonald, KFoxP3(+) confers suppressive properties and is confined to regulatory T cells (T(reg)) that potently inhibit autoreactive immune responses. In the transplant setting, natural CD4(+) T(reg) are critical in controlling alloreactivity and the establishment of tolerance. We now identify an important CD8(+) population of FoxP3(+) T(reg) that convert from CD8(+) conventional donor T cells after allogeneic but not syngeneic bone marrow transplantation. These CD8(+) T(reg) undergo conversion in the mesenteric lymph nodes under the influence of recipient dendritic cells and TGF-β. Importantly, this population is as important for protection from GVHD as the well-studied natural CD4(+)FoxP3(+) population and is more potent in exerting class I-restricted and antigen-specific suppression in vitro and in vivo. Critically, CD8(+)FoxP3(+) T(reg) are exquisitely sensitive to inhibition by cyclosporine but can be massively and specifically expanded in vivo to prevent GVHD by coadministering rapamycin and IL-2 antibody complexes. CD8(+)FoxP3(+) T(reg) thus represent a new regulatory population with considerable potential to preferentially subvert MHC class I-restricted T-cell responses after bone marrow transplantation. |
| spellingShingle | Robb, R Lineburg, K Kuns, R Wilson, Y Raffelt, N Olver, S Varelias, A Alexander, K Teal, B Sparwasser, T Hammerling, G Markey, K Koyama, M Clouston, A Engwerda, C Hill, G MacDonald, K Identification and expansion of highly suppressive CD8(+)FoxP3(+) regulatory T cells after experimental allogeneic bone marrow transplantation. |
| title | Identification and expansion of highly suppressive CD8(+)FoxP3(+) regulatory T cells after experimental allogeneic bone marrow transplantation. |
| title_full | Identification and expansion of highly suppressive CD8(+)FoxP3(+) regulatory T cells after experimental allogeneic bone marrow transplantation. |
| title_fullStr | Identification and expansion of highly suppressive CD8(+)FoxP3(+) regulatory T cells after experimental allogeneic bone marrow transplantation. |
| title_full_unstemmed | Identification and expansion of highly suppressive CD8(+)FoxP3(+) regulatory T cells after experimental allogeneic bone marrow transplantation. |
| title_short | Identification and expansion of highly suppressive CD8(+)FoxP3(+) regulatory T cells after experimental allogeneic bone marrow transplantation. |
| title_sort | identification and expansion of highly suppressive cd8 foxp3 regulatory t cells after experimental allogeneic bone marrow transplantation |
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