Effects of Acute Cytomegalovirus Infection on Rat Islet Allograft Survival
Transplantation of pancreatic islets is a promising therapy for the treatment of type 1 diabetes mellitus. However, long-term islet graft survival rates are still unsatisfactory low. In this study we investigated the role of cytomegalovirus (CMV) in islet allograft failure. STZ-diabetic rats receive...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2011-09-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368910X545077 |
| _version_ | 1818063464287961088 |
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| author | M. J. Smelt Ph.D. B. J. De Haan M. M. Faas B. N. Melgert A. De Haan P. De Vos |
| author_facet | M. J. Smelt Ph.D. B. J. De Haan M. M. Faas B. N. Melgert A. De Haan P. De Vos |
| author_sort | M. J. Smelt Ph.D. |
| collection | DOAJ |
| description | Transplantation of pancreatic islets is a promising therapy for the treatment of type 1 diabetes mellitus. However, long-term islet graft survival rates are still unsatisfactory low. In this study we investigated the role of cytomegalovirus (CMV) in islet allograft failure. STZ-diabetic rats received an allogenic islet graft in combination with either an acute CMV infection or control infection. A third group received ganciclovir treatment in addition to the CMV infection. Graft function was assessed by measuring basal blood glucose levels. After sacrifice, the islet grafts were retrieved for analysis of infection and leukocyte infiltration. CMV-infected recipients demonstrated accelerated islet graft failure compared to noninfected controls. CMV infection of the graft was only observed prior to complete graft failure. Quantification of the leukocyte infiltration demonstrated increased CD8 + T-cell and NK cell infiltration in the CMV-infected grafts compared to the controls. This suggests that CMV infection accelerates immune-mediated graft destruction. Antiviral ganciclovir treatment did not prevent accelerated graft failure, despite effectively decreasing the grade of infection. Our data confirm the recently published CITR data, which state that CMV is an independent risk factor for failure of islet grafts. Also, our data demonstrate that new approaches for preventing virus-induced islet allograft failure may be required. |
| first_indexed | 2024-12-10T14:20:31Z |
| format | Article |
| id | doaj.art-c44422f9250c404f8360a30f67635979 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-10T14:20:31Z |
| publishDate | 2011-09-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-c44422f9250c404f8360a30f676359792022-12-22T01:45:13ZengSAGE PublishingCell Transplantation0963-68971555-38922011-09-012010.3727/096368910X545077Effects of Acute Cytomegalovirus Infection on Rat Islet Allograft SurvivalM. J. Smelt Ph.D.0B. J. De Haan1M. M. Faas2B. N. Melgert3A. De Haan4P. De Vos5 Department of Pathology and Medical Biology, Division of Medical Biology, Section Immunoendocrinology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands Department of Pathology and Medical Biology, Division of Medical Biology, Section Immunoendocrinology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands Department of Pathology and Medical Biology, Division of Medical Biology, Section Immunoendocrinology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands Department of Pathology and Medical Biology, Division of Medical Biology, Section Immunoendocrinology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands Department of Medical Microbiology, Division Molecular Virology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands Department of Pathology and Medical Biology, Division of Medical Biology, Section Immunoendocrinology, University Medical Center Groningen and University of Groningen, Groningen, The NetherlandsTransplantation of pancreatic islets is a promising therapy for the treatment of type 1 diabetes mellitus. However, long-term islet graft survival rates are still unsatisfactory low. In this study we investigated the role of cytomegalovirus (CMV) in islet allograft failure. STZ-diabetic rats received an allogenic islet graft in combination with either an acute CMV infection or control infection. A third group received ganciclovir treatment in addition to the CMV infection. Graft function was assessed by measuring basal blood glucose levels. After sacrifice, the islet grafts were retrieved for analysis of infection and leukocyte infiltration. CMV-infected recipients demonstrated accelerated islet graft failure compared to noninfected controls. CMV infection of the graft was only observed prior to complete graft failure. Quantification of the leukocyte infiltration demonstrated increased CD8 + T-cell and NK cell infiltration in the CMV-infected grafts compared to the controls. This suggests that CMV infection accelerates immune-mediated graft destruction. Antiviral ganciclovir treatment did not prevent accelerated graft failure, despite effectively decreasing the grade of infection. Our data confirm the recently published CITR data, which state that CMV is an independent risk factor for failure of islet grafts. Also, our data demonstrate that new approaches for preventing virus-induced islet allograft failure may be required.https://doi.org/10.3727/096368910X545077 |
| spellingShingle | M. J. Smelt Ph.D. B. J. De Haan M. M. Faas B. N. Melgert A. De Haan P. De Vos Effects of Acute Cytomegalovirus Infection on Rat Islet Allograft Survival Cell Transplantation |
| title | Effects of Acute Cytomegalovirus Infection on Rat Islet Allograft Survival |
| title_full | Effects of Acute Cytomegalovirus Infection on Rat Islet Allograft Survival |
| title_fullStr | Effects of Acute Cytomegalovirus Infection on Rat Islet Allograft Survival |
| title_full_unstemmed | Effects of Acute Cytomegalovirus Infection on Rat Islet Allograft Survival |
| title_short | Effects of Acute Cytomegalovirus Infection on Rat Islet Allograft Survival |
| title_sort | effects of acute cytomegalovirus infection on rat islet allograft survival |
| url | https://doi.org/10.3727/096368910X545077 |
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