B7-H4 Pathway in Islet Transplantation and β-Cell Replacement Therapies
Type 1 diabetes (T1D) is a chronic autoimmune disease and characterized by absolute insulin deficiency. β-cell replacement by islet cell transplantation has been established as a feasible treatment option for T1D. The two main obstacles after islet transplantation are alloreactive T-cell-mediated gr...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Journal of Transplantation |
| Online Access: | http://dx.doi.org/10.1155/2011/418902 |
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| author | Xiaojie Wang Jianqiang Hao Daniel L. Metzger Ziliang Ao Mark Meloche C. Bruce Verchere Lieping Chen Dawei Ou Alice Mui Garth L. Warnock |
| author_facet | Xiaojie Wang Jianqiang Hao Daniel L. Metzger Ziliang Ao Mark Meloche C. Bruce Verchere Lieping Chen Dawei Ou Alice Mui Garth L. Warnock |
| author_sort | Xiaojie Wang |
| collection | DOAJ |
| description | Type 1 diabetes (T1D) is a chronic autoimmune disease and characterized by absolute insulin deficiency. β-cell replacement by islet cell transplantation has been established as a feasible treatment option for T1D. The two main obstacles after islet transplantation are alloreactive T-cell-mediated graft rejection and recurrence of autoimmune diabetes mellitus in recipients. T cells play a central role in determining the outcome of both autoimmune responses and allograft survival. B7-H4, a newly identified B7 homolog, plays a key role in maintaining T-cell homeostasis by reducing T-cell proliferation and cytokine production. The relationship between B7-H4 and allograft survival/autoimmunity has been investigated recently in both islet transplantation and the nonobese diabetic (NOD) mouse models. B7-H4 protects allograft survival and generates donor-specific tolerance. It also prevents the development of autoimmune diabetes. More importantly, B7-H4 plays an indispensable role in alloimmunity in the absence of the classic CD28/CTLA-4 : B7 pathway, suggesting a synergistic/additive effect with other agents such as CTLA-4 on inhibition of unwanted immune responses. |
| format | Article |
| id | doaj-art-a65e6589fd094c0ab878c5d910be7c30 |
| institution | Kabale University |
| issn | 2090-0007 2090-0015 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Transplantation |
| spelling | doaj-art-a65e6589fd094c0ab878c5d910be7c302025-02-03T01:02:54ZengWileyJournal of Transplantation2090-00072090-00152011-01-01201110.1155/2011/418902418902B7-H4 Pathway in Islet Transplantation and β-Cell Replacement TherapiesXiaojie Wang0Jianqiang Hao1Daniel L. Metzger2Ziliang Ao3Mark Meloche4C. Bruce Verchere5Lieping Chen6Dawei Ou7Alice Mui8Garth L. Warnock9Department of Surgery, University of British Columbia, Vancouver, BC, V5Z 4E3, CanadaDepartment of Surgery, University of British Columbia, Vancouver, BC, V5Z 4E3, CanadaDepartment of Paediatrics, University of British Columbia, Vancouver, BC, V6H 3V4, CanadaDepartment of Surgery, University of British Columbia, Vancouver, BC, V5Z 4E3, CanadaDepartment of Surgery, University of British Columbia, Vancouver, BC, V5Z 4E3, CanadaDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, V5Z 4H4, CanadaDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USADepartment of Surgery, University of British Columbia, Vancouver, BC, V5Z 4E3, CanadaDepartment of Surgery, University of British Columbia, Vancouver, BC, V5Z 4E3, CanadaDepartment of Surgery, University of British Columbia, Vancouver, BC, V5Z 4E3, CanadaType 1 diabetes (T1D) is a chronic autoimmune disease and characterized by absolute insulin deficiency. β-cell replacement by islet cell transplantation has been established as a feasible treatment option for T1D. The two main obstacles after islet transplantation are alloreactive T-cell-mediated graft rejection and recurrence of autoimmune diabetes mellitus in recipients. T cells play a central role in determining the outcome of both autoimmune responses and allograft survival. B7-H4, a newly identified B7 homolog, plays a key role in maintaining T-cell homeostasis by reducing T-cell proliferation and cytokine production. The relationship between B7-H4 and allograft survival/autoimmunity has been investigated recently in both islet transplantation and the nonobese diabetic (NOD) mouse models. B7-H4 protects allograft survival and generates donor-specific tolerance. It also prevents the development of autoimmune diabetes. More importantly, B7-H4 plays an indispensable role in alloimmunity in the absence of the classic CD28/CTLA-4 : B7 pathway, suggesting a synergistic/additive effect with other agents such as CTLA-4 on inhibition of unwanted immune responses.http://dx.doi.org/10.1155/2011/418902 |
| spellingShingle | Xiaojie Wang Jianqiang Hao Daniel L. Metzger Ziliang Ao Mark Meloche C. Bruce Verchere Lieping Chen Dawei Ou Alice Mui Garth L. Warnock B7-H4 Pathway in Islet Transplantation and β-Cell Replacement Therapies Journal of Transplantation |
| title | B7-H4 Pathway in Islet Transplantation and β-Cell Replacement Therapies |
| title_full | B7-H4 Pathway in Islet Transplantation and β-Cell Replacement Therapies |
| title_fullStr | B7-H4 Pathway in Islet Transplantation and β-Cell Replacement Therapies |
| title_full_unstemmed | B7-H4 Pathway in Islet Transplantation and β-Cell Replacement Therapies |
| title_short | B7-H4 Pathway in Islet Transplantation and β-Cell Replacement Therapies |
| title_sort | b7 h4 pathway in islet transplantation and β cell replacement therapies |
| url | http://dx.doi.org/10.1155/2011/418902 |
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