Donor-specific Regulatory T Cells Acquired from Tolerant Mice Bearing Cardiac allograft Promote Mixed Chimerism and Prolong Intestinal Allograft Survival
The induction of donor-specific transplant tolerance has always been a central problem for small bowel transplantation, which is thought to be the best therapy for end-stage bowel failure. With the development of new tolerance-inducing strategies, mixed chimerism induced by co-stimulation blockade h...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00511/full |
| _version_ | 1819266713262227456 |
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| author | Xiaofei Shen Jinpeng Jiang Jianjun Yang Weizhong Wang Junfeng Du Wenxian Guan |
| author_facet | Xiaofei Shen Jinpeng Jiang Jianjun Yang Weizhong Wang Junfeng Du Wenxian Guan |
| author_sort | Xiaofei Shen |
| collection | DOAJ |
| description | The induction of donor-specific transplant tolerance has always been a central problem for small bowel transplantation, which is thought to be the best therapy for end-stage bowel failure. With the development of new tolerance-inducing strategies, mixed chimerism induced by co-stimulation blockade has become most potent for tolerance of allografts such as skin, kidney and heart. However, a lack of clinically available co-stimulation blockers has hindered efficient application in humans. Furthermore, unlike those for other types of solid organ transplantation, strategies to induce robust mixed chimerism for intestinal allografts have not been fully developed. To improve current mixed chimerism induction protocols for future clinical application, we developed a new protocol using donor-specific regulatory T (Treg) cells from mice with heart allograft tolerance, clinically available immunosuppressive drugs, and low doses of irradiation. Our results demonstrated that donor-specific Treg cells acquired from tolerant mice after in vitro expansion generate stable chimerism and lead to acceptance of intestinal allograft. Increased intragraft Treg cells and clonal deletion both contribute to the development of small bowel transplantation tolerance. |
| first_indexed | 2024-12-23T21:05:39Z |
| format | Article |
| id | doaj.art-3bd8c4ff34d34b029f38a809c19015fa |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T21:05:39Z |
| publishDate | 2016-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3bd8c4ff34d34b029f38a809c19015fa2022-12-21T17:31:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242016-11-01710.3389/fimmu.2016.00511221160Donor-specific Regulatory T Cells Acquired from Tolerant Mice Bearing Cardiac allograft Promote Mixed Chimerism and Prolong Intestinal Allograft SurvivalXiaofei Shen0Jinpeng Jiang1Jianjun Yang2Weizhong Wang3Junfeng Du4Wenxian Guan5Affiliated Drum Tower Hospital of Nanjing University Medical SchoolPLA Army General HospitalXijing Hospital of Digestive DiseasesXijing Hospital of Digestive DiseasesPLA Army General HospitalAffiliated Drum Tower Hospital of Nanjing University Medical SchoolThe induction of donor-specific transplant tolerance has always been a central problem for small bowel transplantation, which is thought to be the best therapy for end-stage bowel failure. With the development of new tolerance-inducing strategies, mixed chimerism induced by co-stimulation blockade has become most potent for tolerance of allografts such as skin, kidney and heart. However, a lack of clinically available co-stimulation blockers has hindered efficient application in humans. Furthermore, unlike those for other types of solid organ transplantation, strategies to induce robust mixed chimerism for intestinal allografts have not been fully developed. To improve current mixed chimerism induction protocols for future clinical application, we developed a new protocol using donor-specific regulatory T (Treg) cells from mice with heart allograft tolerance, clinically available immunosuppressive drugs, and low doses of irradiation. Our results demonstrated that donor-specific Treg cells acquired from tolerant mice after in vitro expansion generate stable chimerism and lead to acceptance of intestinal allograft. Increased intragraft Treg cells and clonal deletion both contribute to the development of small bowel transplantation tolerance.http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00511/fullBone Marrow TransplantationTransplantation Tolerancemixed chimerismSmall bowel transplantationdonor-specific regulatory T cells |
| spellingShingle | Xiaofei Shen Jinpeng Jiang Jianjun Yang Weizhong Wang Junfeng Du Wenxian Guan Donor-specific Regulatory T Cells Acquired from Tolerant Mice Bearing Cardiac allograft Promote Mixed Chimerism and Prolong Intestinal Allograft Survival Frontiers in Immunology Bone Marrow Transplantation Transplantation Tolerance mixed chimerism Small bowel transplantation donor-specific regulatory T cells |
| title | Donor-specific Regulatory T Cells Acquired from Tolerant Mice Bearing Cardiac allograft Promote Mixed Chimerism and Prolong Intestinal Allograft Survival |
| title_full | Donor-specific Regulatory T Cells Acquired from Tolerant Mice Bearing Cardiac allograft Promote Mixed Chimerism and Prolong Intestinal Allograft Survival |
| title_fullStr | Donor-specific Regulatory T Cells Acquired from Tolerant Mice Bearing Cardiac allograft Promote Mixed Chimerism and Prolong Intestinal Allograft Survival |
| title_full_unstemmed | Donor-specific Regulatory T Cells Acquired from Tolerant Mice Bearing Cardiac allograft Promote Mixed Chimerism and Prolong Intestinal Allograft Survival |
| title_short | Donor-specific Regulatory T Cells Acquired from Tolerant Mice Bearing Cardiac allograft Promote Mixed Chimerism and Prolong Intestinal Allograft Survival |
| title_sort | donor specific regulatory t cells acquired from tolerant mice bearing cardiac allograft promote mixed chimerism and prolong intestinal allograft survival |
| topic | Bone Marrow Transplantation Transplantation Tolerance mixed chimerism Small bowel transplantation donor-specific regulatory T cells |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00511/full |
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