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Murine cytomegalovirus dissemination but not reactivation in donor-positive/recipient-negative allogeneic kidney transplantation can be effectively prevented by transplant immune tolerance.

Publication ,  Journal Article
Dangi, A; Yu, S; Lee, FT; Burnette, M; Wang, J-J; Kanwar, YS; Zhang, ZJ; Abecassis, M; Thorp, EB; Luo, X
Published in: Kidney international
July 2020

Cytomegalovirus (CMV) reactivation from latently infected donor organs post-transplantation and its dissemination cause significant comorbidities in transplant recipients. Transplant-induced inflammation combined with chronic immunosuppression has been thought to provoke CMV reactivation and dissemination, although sequential events in this process have not been studied. Here, we investigated this process in a high-risk donor CMV-positive to recipient CMV-negative allogeneic murine kidney transplantation model. Recipients were either treated with indefinite immunosuppression or tolerized in a donor-specific manner. Untreated recipients served as controls. Kidney allografts from both immunosuppressed and tolerized recipients showed minimal alloimmunity-mediated graft inflammation and normal function for up to day 60 post-transplantation. However, despite the absence of such inflammation in the immunosuppressed and tolerized groups, CMV reactivation in the donor positive kidney allograft was readily observed. Interestingly, subsequent CMV replication and dissemination to distant organs only occurred in immunosuppressed recipients in which CMV-specific CD8 T cells were functionally impaired; whereas in tolerized recipients, host anti-viral immunity was well-preserved and CMV dissemination was effectively prevented. Thus, our studies uncoupled CMV reactivation from its dissemination, and underscore the potential role of robust transplantation tolerance in preventing CMV diseases following allogeneic kidney transplantation.

Duke Scholars

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Published In

Kidney international

DOI

EISSN

1523-1755

ISSN

0085-2538

Publication Date

July 2020

Volume

98

Issue

1

Start / End Page

147 / 158

Related Subject Headings

  • Virus Activation
  • Urology & Nephrology
  • Transplantation Tolerance
  • Muromegalovirus
  • Mice
  • Kidney Transplantation
  • Kidney
  • Immune Tolerance
  • Hematopoietic Stem Cell Transplantation
  • Cytomegalovirus
 

Citation

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ICMJE
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Dangi, A., Yu, S., Lee, F. T., Burnette, M., Wang, J.-J., Kanwar, Y. S., … Luo, X. (2020). Murine cytomegalovirus dissemination but not reactivation in donor-positive/recipient-negative allogeneic kidney transplantation can be effectively prevented by transplant immune tolerance. Kidney International, 98(1), 147–158. https://doi.org/10.1016/j.kint.2020.01.034
Dangi, Anil, Shuangjin Yu, Frances T. Lee, Melanie Burnette, Jiao-Jing Wang, Yashpal S. Kanwar, Zheng J. Zhang, Michael Abecassis, Edward B. Thorp, and Xunrong Luo. “Murine cytomegalovirus dissemination but not reactivation in donor-positive/recipient-negative allogeneic kidney transplantation can be effectively prevented by transplant immune tolerance.Kidney International 98, no. 1 (July 2020): 147–58. https://doi.org/10.1016/j.kint.2020.01.034.
Dangi, Anil, et al. “Murine cytomegalovirus dissemination but not reactivation in donor-positive/recipient-negative allogeneic kidney transplantation can be effectively prevented by transplant immune tolerance.Kidney International, vol. 98, no. 1, July 2020, pp. 147–58. Epmc, doi:10.1016/j.kint.2020.01.034.
Dangi A, Yu S, Lee FT, Burnette M, Wang J-J, Kanwar YS, Zhang ZJ, Abecassis M, Thorp EB, Luo X. Murine cytomegalovirus dissemination but not reactivation in donor-positive/recipient-negative allogeneic kidney transplantation can be effectively prevented by transplant immune tolerance. Kidney international. 2020 Jul;98(1):147–158.
Journal cover image

Published In

Kidney international

DOI

EISSN

1523-1755

ISSN

0085-2538

Publication Date

July 2020

Volume

98

Issue

1

Start / End Page

147 / 158

Related Subject Headings

  • Virus Activation
  • Urology & Nephrology
  • Transplantation Tolerance
  • Muromegalovirus
  • Mice
  • Kidney Transplantation
  • Kidney
  • Immune Tolerance
  • Hematopoietic Stem Cell Transplantation
  • Cytomegalovirus