Allograft rejection mediated by memory T cells is resistant to regulation.
Alloreactive memory T cells may be refractory to many of the tolerance-inducing strategies that are effective against naive T cells and thus present a significant barrier to long-term allograft survival. Because CD4(+)CD25(+) regulatory T cells (Tregs) are critical elements of many approaches to suc...
| Glavni autori: | , , , , , , , , |
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| Format: | Journal article |
| Jezik: | English |
| Izdano: |
2007
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| _version_ | 1826295451549171712 |
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| author | Yang, J Brook, M Carvalho-Gaspar, M Zhang, J Ramon, H Sayegh, M Wood, K Turka, L Jones, N |
| author_facet | Yang, J Brook, M Carvalho-Gaspar, M Zhang, J Ramon, H Sayegh, M Wood, K Turka, L Jones, N |
| author_sort | Yang, J |
| collection | OXFORD |
| description | Alloreactive memory T cells may be refractory to many of the tolerance-inducing strategies that are effective against naive T cells and thus present a significant barrier to long-term allograft survival. Because CD4(+)CD25(+) regulatory T cells (Tregs) are critical elements of many approaches to successful induction/maintenance of transplantation tolerance, we used MHC class I and II alloreactive TCR-transgenic models to explore the ability of antigen-specific Tregs to control antigen-specific memory T cell responses. Upon coadoptive transfer into RAG-1(-/-) mice, we found that Tregs effectively suppressed the ability of naive T cells to reject skin grafts, but neither antigen-unprimed nor antigen-primed Tregs suppressed rejection by memory T cells. Interestingly, different mechanisms appeared to be active in the ability of Tregs to control naive T cell-mediated graft rejection in the class II versus class I alloreactive models. In the former case, we observed decreased early expansion of effector cells in lymphoid tissue. In contrast, in the class I model, an effect of Tregs on early proliferation and expansion was not observed. However, at a late time point, significant differences in cell numbers were seen, suggesting effects on responding T cell survival. Overall, these data indicate that the relative resistance of both CD4(+) and CD8(+) alloreactive memory T cells to regulation may mediate resistance to tolerance induction seen in hosts with preexisting alloantigen-specific immunity and further indicate the multiplicity of mechanisms by which Tregs may control alloimmune responses in vivo. |
| first_indexed | 2024-03-07T04:01:15Z |
| format | Journal article |
| id | oxford-uuid:c4a5ae4e-336c-414e-9d4e-889babc804a6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:01:15Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:c4a5ae4e-336c-414e-9d4e-889babc804a62022-03-27T06:25:06ZAllograft rejection mediated by memory T cells is resistant to regulation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c4a5ae4e-336c-414e-9d4e-889babc804a6EnglishSymplectic Elements at Oxford2007Yang, JBrook, MCarvalho-Gaspar, MZhang, JRamon, HSayegh, MWood, KTurka, LJones, NAlloreactive memory T cells may be refractory to many of the tolerance-inducing strategies that are effective against naive T cells and thus present a significant barrier to long-term allograft survival. Because CD4(+)CD25(+) regulatory T cells (Tregs) are critical elements of many approaches to successful induction/maintenance of transplantation tolerance, we used MHC class I and II alloreactive TCR-transgenic models to explore the ability of antigen-specific Tregs to control antigen-specific memory T cell responses. Upon coadoptive transfer into RAG-1(-/-) mice, we found that Tregs effectively suppressed the ability of naive T cells to reject skin grafts, but neither antigen-unprimed nor antigen-primed Tregs suppressed rejection by memory T cells. Interestingly, different mechanisms appeared to be active in the ability of Tregs to control naive T cell-mediated graft rejection in the class II versus class I alloreactive models. In the former case, we observed decreased early expansion of effector cells in lymphoid tissue. In contrast, in the class I model, an effect of Tregs on early proliferation and expansion was not observed. However, at a late time point, significant differences in cell numbers were seen, suggesting effects on responding T cell survival. Overall, these data indicate that the relative resistance of both CD4(+) and CD8(+) alloreactive memory T cells to regulation may mediate resistance to tolerance induction seen in hosts with preexisting alloantigen-specific immunity and further indicate the multiplicity of mechanisms by which Tregs may control alloimmune responses in vivo. |
| spellingShingle | Yang, J Brook, M Carvalho-Gaspar, M Zhang, J Ramon, H Sayegh, M Wood, K Turka, L Jones, N Allograft rejection mediated by memory T cells is resistant to regulation. |
| title | Allograft rejection mediated by memory T cells is resistant to regulation. |
| title_full | Allograft rejection mediated by memory T cells is resistant to regulation. |
| title_fullStr | Allograft rejection mediated by memory T cells is resistant to regulation. |
| title_full_unstemmed | Allograft rejection mediated by memory T cells is resistant to regulation. |
| title_short | Allograft rejection mediated by memory T cells is resistant to regulation. |
| title_sort | allograft rejection mediated by memory t cells is resistant to regulation |
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