CD8+ T Cells Protect During Vein Graft Disease Development
Aims: Vein grafts are frequently used conduits for arterial reconstruction in patients with cardiovascular disease. Unfortunately, vein graft disease (VGD) causes diminished patency rates. Innate immune system components are known to contribute to VGD. However, the role of T cells has yet to be esta...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-06-01
|
| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcvm.2019.00077/full |
| _version_ | 1811327604645429248 |
|---|---|
| author | Karin H. Simons Karin H. Simons Margreet R. de Vries Margreet R. de Vries Hendrika A. B. Peters Hendrika A. B. Peters J. Wouter Jukema J. Wouter Jukema Paul H. A. Quax Paul H. A. Quax Ramon Arens |
| author_facet | Karin H. Simons Karin H. Simons Margreet R. de Vries Margreet R. de Vries Hendrika A. B. Peters Hendrika A. B. Peters J. Wouter Jukema J. Wouter Jukema Paul H. A. Quax Paul H. A. Quax Ramon Arens |
| author_sort | Karin H. Simons |
| collection | DOAJ |
| description | Aims: Vein grafts are frequently used conduits for arterial reconstruction in patients with cardiovascular disease. Unfortunately, vein graft disease (VGD) causes diminished patency rates. Innate immune system components are known to contribute to VGD. However, the role of T cells has yet to be established. The purpose of this study was to investigate the role of T cells and T cell activation pathways via the T cell receptor (TCR), co-stimulation and bystander effect in VGD.Methods and results: Here, we show upon vein graft surgery in mice depleted of CD4+ T cells or CD8+ T cells, that CD8+ T cells are locally activated and have a major protective role for vein graft patency. In presence of CD8+ T cells vein grafts appear patent while CD8+ T cell depletion results in occluded vein grafts with increases apoptosis. Importantly, the protective effect of CD8+ T cells in VGD development was TCR and co-stimulation independent. This was demonstrated in vein grafts of OT-I mice, CD70−/−, CD80/86−/−, and CD70/80/86−/− mice compared to C57BL/6 mice. Interestingly, cytokines including IL-15, IL-18, IL-33, and TNF are up-regulated in vein grafts. These cytokines are co-operatively capable to activate CD8+ T cells in a bystander-mediated fashion, in contrast to CD4+ T cells.Conclusions: T cells are modulators of VGD with a specific protective role of CD8+ T cells, which are locally activated in vein grafts. CD8+ T cells may protect against occlusive lesions by providing survival signals, and concert their protection independent of TCR and co-stimulation signaling. |
| first_indexed | 2024-04-13T15:09:42Z |
| format | Article |
| id | doaj.art-2a8ada1a2d364c178466a359c5850df5 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-13T15:09:42Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-2a8ada1a2d364c178466a359c5850df52022-12-22T02:42:02ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2019-06-01610.3389/fcvm.2019.00077461927CD8+ T Cells Protect During Vein Graft Disease DevelopmentKarin H. Simons0Karin H. Simons1Margreet R. de Vries2Margreet R. de Vries3Hendrika A. B. Peters4Hendrika A. B. Peters5J. Wouter Jukema6J. Wouter Jukema7Paul H. A. Quax8Paul H. A. Quax9Ramon Arens10Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, NetherlandsDepartment of Surgery, Leiden University Medical Center, Leiden, NetherlandsEinthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, NetherlandsDepartment of Surgery, Leiden University Medical Center, Leiden, NetherlandsEinthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, NetherlandsDepartment of Surgery, Leiden University Medical Center, Leiden, NetherlandsEinthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, NetherlandsDepartment of Cardiology, Leiden University Medical Center, Leiden, NetherlandsEinthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, NetherlandsDepartment of Surgery, Leiden University Medical Center, Leiden, NetherlandsDepartment of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, NetherlandsAims: Vein grafts are frequently used conduits for arterial reconstruction in patients with cardiovascular disease. Unfortunately, vein graft disease (VGD) causes diminished patency rates. Innate immune system components are known to contribute to VGD. However, the role of T cells has yet to be established. The purpose of this study was to investigate the role of T cells and T cell activation pathways via the T cell receptor (TCR), co-stimulation and bystander effect in VGD.Methods and results: Here, we show upon vein graft surgery in mice depleted of CD4+ T cells or CD8+ T cells, that CD8+ T cells are locally activated and have a major protective role for vein graft patency. In presence of CD8+ T cells vein grafts appear patent while CD8+ T cell depletion results in occluded vein grafts with increases apoptosis. Importantly, the protective effect of CD8+ T cells in VGD development was TCR and co-stimulation independent. This was demonstrated in vein grafts of OT-I mice, CD70−/−, CD80/86−/−, and CD70/80/86−/− mice compared to C57BL/6 mice. Interestingly, cytokines including IL-15, IL-18, IL-33, and TNF are up-regulated in vein grafts. These cytokines are co-operatively capable to activate CD8+ T cells in a bystander-mediated fashion, in contrast to CD4+ T cells.Conclusions: T cells are modulators of VGD with a specific protective role of CD8+ T cells, which are locally activated in vein grafts. CD8+ T cells may protect against occlusive lesions by providing survival signals, and concert their protection independent of TCR and co-stimulation signaling.https://www.frontiersin.org/article/10.3389/fcvm.2019.00077/fullT cellco-stimulationCD8+ activationvein graft diseasevein graft failureTCR–T cell receptor |
| spellingShingle | Karin H. Simons Karin H. Simons Margreet R. de Vries Margreet R. de Vries Hendrika A. B. Peters Hendrika A. B. Peters J. Wouter Jukema J. Wouter Jukema Paul H. A. Quax Paul H. A. Quax Ramon Arens CD8+ T Cells Protect During Vein Graft Disease Development Frontiers in Cardiovascular Medicine T cell co-stimulation CD8+ activation vein graft disease vein graft failure TCR–T cell receptor |
| title | CD8+ T Cells Protect During Vein Graft Disease Development |
| title_full | CD8+ T Cells Protect During Vein Graft Disease Development |
| title_fullStr | CD8+ T Cells Protect During Vein Graft Disease Development |
| title_full_unstemmed | CD8+ T Cells Protect During Vein Graft Disease Development |
| title_short | CD8+ T Cells Protect During Vein Graft Disease Development |
| title_sort | cd8 t cells protect during vein graft disease development |
| topic | T cell co-stimulation CD8+ activation vein graft disease vein graft failure TCR–T cell receptor |
| url | https://www.frontiersin.org/article/10.3389/fcvm.2019.00077/full |
| work_keys_str_mv | AT karinhsimons cd8tcellsprotectduringveingraftdiseasedevelopment AT karinhsimons cd8tcellsprotectduringveingraftdiseasedevelopment AT margreetrdevries cd8tcellsprotectduringveingraftdiseasedevelopment AT margreetrdevries cd8tcellsprotectduringveingraftdiseasedevelopment AT hendrikaabpeters cd8tcellsprotectduringveingraftdiseasedevelopment AT hendrikaabpeters cd8tcellsprotectduringveingraftdiseasedevelopment AT jwouterjukema cd8tcellsprotectduringveingraftdiseasedevelopment AT jwouterjukema cd8tcellsprotectduringveingraftdiseasedevelopment AT paulhaquax cd8tcellsprotectduringveingraftdiseasedevelopment AT paulhaquax cd8tcellsprotectduringveingraftdiseasedevelopment AT ramonarens cd8tcellsprotectduringveingraftdiseasedevelopment |