Effects of acute cytomegalovirus infection on rat islet allograft survival

M J Smelt, B J de Haan, M M Faas, B N Melgert, A de Haan, P de Vos

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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. © 2011 Cognizant Comm. Corp.
Original languageEnglish
Pages (from-to)1271-1283
Number of pages13
JournalCell transplantation
Volume20
Issue number8
DOIs
Publication statusPublished - 2011
Externally publishedYes

Fingerprint

Cytomegalovirus Infections
Grafts
Allografts
Rats
Transplants
Cytomegalovirus
Infiltration
Ganciclovir
Leukocytes
Infection
Islets of Langerhans Transplantation
T-cells
Graft Survival
Therapeutics
Infection Control
Type 1 Diabetes Mellitus
Natural Killer Cells
Medical problems
Viruses
Antiviral Agents

Keywords

  • Animals
  • Antiviral Agents/pharmacology
  • Blood Glucose/drug effects
  • Cell Movement/drug effects
  • Cytomegalovirus/drug effects
  • Cytomegalovirus Infections/immunology
  • Ganciclovir/pharmacology
  • Graft Survival/drug effects
  • Immunity/drug effects
  • Islets of Langerhans Transplantation/immunology
  • Rats
  • Rats, Inbred Lew
  • Salivary Glands/drug effects
  • Transplantation, Homologous

Cite this

Smelt, M. J., de Haan, B. J., Faas, M. M., Melgert, B. N., de Haan, A., & de Vos, P. (2011). Effects of acute cytomegalovirus infection on rat islet allograft survival. Cell transplantation, 20(8), 1271-1283. https://doi.org/10.3727/096368910X545077
Smelt, M J ; de Haan, B J ; Faas, M M ; Melgert, B N ; de Haan, A ; de Vos, P. / Effects of acute cytomegalovirus infection on rat islet allograft survival. In: Cell transplantation. 2011 ; Vol. 20, No. 8. pp. 1271-1283.
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Smelt, MJ, de Haan, BJ, Faas, MM, Melgert, BN, de Haan, A & de Vos, P 2011, 'Effects of acute cytomegalovirus infection on rat islet allograft survival', Cell transplantation, vol. 20, no. 8, pp. 1271-1283. https://doi.org/10.3727/096368910X545077

Effects of acute cytomegalovirus infection on rat islet allograft survival. / Smelt, M J; de Haan, B J; Faas, M M; Melgert, B N; de Haan, A; de Vos, P.

In: Cell transplantation, Vol. 20, No. 8, 2011, p. 1271-1283.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Effects of acute cytomegalovirus infection on rat islet allograft survival

AU - Smelt, M J

AU - de Haan, B J

AU - Faas, M M

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AU - de Vos, P

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AB - 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. © 2011 Cognizant Comm. Corp.

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KW - Rats

KW - Rats, Inbred Lew

KW - Salivary Glands/drug effects

KW - Transplantation, Homologous

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