Simultaneous transplantation of hematopoietic stem cells and a vascularized composite allograft leads to tolerance
BACKGROUND: We have previously demonstrated that tolerance to a vascularized composite allograft (VCA) can be achieved after the establishment of mixed chimerism. We test the hypothesis that tolerance to a VCA in our dog leukocyte antigen-matched canine model is not dependent on the previous establishment of mixed chimerism and can be induced coincident with hematopoietic cell transplantation (HCT).
METHODS: Eight dog leukocyte antigen-matched, minor antigen mismatched dogs received 200 cGy of radiation and a VCA transplant. Four dogs received donor bone marrow at the time of VCA transplantation (group 1), whereas a second group of four dogs did not (group 2). All recipients received a limited course of postgrafting immunosuppression. All dogs that received HCT and VCA were given donor, third-party, and autologous skin grafts.
RESULTS: All group 1 recipients were tolerant to their VCA (>62 weeks). Three of the four dogs in group 2 rejected their VCA transplants after the cessation of immunosuppression. Biopsies obtained from the muscle and skin of VCA from group 1 showed few infiltrating cells compared with extensive infiltrates in biopsies of VCA from group 2. Compared with autologous skin and muscle, elevated levels of CD3+ FoxP3+ T-regulatory cells were found in the skin and muscle obtained from the VCA of HCT recipients. All group 1 animals were tolerant to their donor skin graft and promptly rejected the third-party skin grafts.
CONCLUSION: These data demonstrated that donor-specific tolerance to all components of the VCA can be established through simultaneous nonmyeloablative allogeneic HCT and VCA transplantation protocol.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:98 |
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| Enthalten in: |
Transplantation - 98(2014), 2 vom: 27. Juli, Seite 131-8 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mathes, David W [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.09.2014 Date Revised 21.10.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1097/TP.0000000000000204 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM23908280X |
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| 100 | 1 | |a Mathes, David W |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Simultaneous transplantation of hematopoietic stem cells and a vascularized composite allograft leads to tolerance |
| 264 | 1 | |c 2014 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 08.09.2014 | ||
| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: We have previously demonstrated that tolerance to a vascularized composite allograft (VCA) can be achieved after the establishment of mixed chimerism. We test the hypothesis that tolerance to a VCA in our dog leukocyte antigen-matched canine model is not dependent on the previous establishment of mixed chimerism and can be induced coincident with hematopoietic cell transplantation (HCT) | ||
| 520 | |a METHODS: Eight dog leukocyte antigen-matched, minor antigen mismatched dogs received 200 cGy of radiation and a VCA transplant. Four dogs received donor bone marrow at the time of VCA transplantation (group 1), whereas a second group of four dogs did not (group 2). All recipients received a limited course of postgrafting immunosuppression. All dogs that received HCT and VCA were given donor, third-party, and autologous skin grafts | ||
| 520 | |a RESULTS: All group 1 recipients were tolerant to their VCA (>62 weeks). Three of the four dogs in group 2 rejected their VCA transplants after the cessation of immunosuppression. Biopsies obtained from the muscle and skin of VCA from group 1 showed few infiltrating cells compared with extensive infiltrates in biopsies of VCA from group 2. Compared with autologous skin and muscle, elevated levels of CD3+ FoxP3+ T-regulatory cells were found in the skin and muscle obtained from the VCA of HCT recipients. All group 1 animals were tolerant to their donor skin graft and promptly rejected the third-party skin grafts | ||
| 520 | |a CONCLUSION: These data demonstrated that donor-specific tolerance to all components of the VCA can be established through simultaneous nonmyeloablative allogeneic HCT and VCA transplantation protocol | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a CD3 Complex |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Forkhead Transcription Factors |2 NLM | |
| 650 | 7 | |a Histocompatibility Antigens |2 NLM | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 650 | 7 | |a Myeloablative Agonists |2 NLM | |
| 700 | 1 | |a Chang, Jeff |e verfasserin |4 aut | |
| 700 | 1 | |a Hwang, Billanna |e verfasserin |4 aut | |
| 700 | 1 | |a Graves, Scott S |e verfasserin |4 aut | |
| 700 | 1 | |a Storer, Barry E |e verfasserin |4 aut | |
| 700 | 1 | |a Butts-Miwongtum, Tiffany |e verfasserin |4 aut | |
| 700 | 1 | |a Sale, George E |e verfasserin |4 aut | |
| 700 | 1 | |a Storb, Rainer |e verfasserin |4 aut | |
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