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MCMV Dissemination from Latently-Infected Allografts Following Transplantation into Pre-Tolerized Recipients.

Publication ,  Journal Article
Shah, S; DeBerge, M; Iovane, A; Yan, S; Qiu, L; Wang, J-J; Kanwar, YS; Hummel, M; Zhang, ZJ; Abecassis, MM; Luo, X; Thorp, EB
Published in: Pathogens (Basel, Switzerland)
July 2020

Transplantation tolerance is achieved when recipients are unresponsive to donor alloantigen yet mobilize against third-party antigens, including virus. After transplantation, cytomegalovirus (CMV) reactivation in latently-infected transplants reduces allograft viability. To determine if pre-tolerized recipients are resistant to viral dissemination in this setting, we transfused chemically-fixed donor splenocytes (1-ethyl-3- (3'-dimethyl-aminopropyl)-carbo-diimide (ECDI)-treated splenocytes (ECDIsp)) to induce donor antigen tolerance without immunosuppression. In parallel, we implanted donor islet cells to validate operational tolerance. These pre-tolerized recipients were implanted with murine CMV (MCMV) latently-infected donor kidneys (a validated model of CMV latency) to monitor graft inflammation and viral dissemination. Our results indicate that tolerance to donor islets was sustained in recipients after implantation of donor kidneys. In addition, kidney allografts implanted after ECDIsp and islet implantation exhibited low levels of fibrosis and tubulitis. In contrast, kidney cellular and innate immune infiltrates trended higher in the CMV group and exhibited increased markers of CD8+ T cell activation. Tolerance induction was unable to prevent increases in MCMV-specific CD8+ T cells or dissemination of viral IE-1 DNA. Our data suggest that latently-infected allografts are inherently more susceptible to inflammation that is associated with viral dissemination in pre-tolerized recipients. Thus, CMV latently-infected allografts require enhanced strategies to protect allograft integrity and viral spread.

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Published In

Pathogens (Basel, Switzerland)

DOI

EISSN

2076-0817

ISSN

2076-0817

Publication Date

July 2020

Volume

9

Issue

8

Start / End Page

E607

Related Subject Headings

  • 3207 Medical microbiology
  • 3204 Immunology
  • 3107 Microbiology
  • 1108 Medical Microbiology
  • 1107 Immunology
 

Citation

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MLA
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Shah, S., DeBerge, M., Iovane, A., Yan, S., Qiu, L., Wang, J.-J., … Thorp, E. B. (2020). MCMV Dissemination from Latently-Infected Allografts Following Transplantation into Pre-Tolerized Recipients. Pathogens (Basel, Switzerland), 9(8), E607. https://doi.org/10.3390/pathogens9080607
Shah, Sahil, Matthew DeBerge, Andre Iovane, Shixian Yan, Longhui Qiu, Jiao-Jing Wang, Yashpal S. Kanwar, et al. “MCMV Dissemination from Latently-Infected Allografts Following Transplantation into Pre-Tolerized Recipients.Pathogens (Basel, Switzerland) 9, no. 8 (July 2020): E607. https://doi.org/10.3390/pathogens9080607.
Shah S, DeBerge M, Iovane A, Yan S, Qiu L, Wang J-J, et al. MCMV Dissemination from Latently-Infected Allografts Following Transplantation into Pre-Tolerized Recipients. Pathogens (Basel, Switzerland). 2020 Jul;9(8):E607.
Shah, Sahil, et al. “MCMV Dissemination from Latently-Infected Allografts Following Transplantation into Pre-Tolerized Recipients.Pathogens (Basel, Switzerland), vol. 9, no. 8, July 2020, p. E607. Epmc, doi:10.3390/pathogens9080607.
Shah S, DeBerge M, Iovane A, Yan S, Qiu L, Wang J-J, Kanwar YS, Hummel M, Zhang ZJ, Abecassis MM, Luo X, Thorp EB. MCMV Dissemination from Latently-Infected Allografts Following Transplantation into Pre-Tolerized Recipients. Pathogens (Basel, Switzerland). 2020 Jul;9(8):E607.

Published In

Pathogens (Basel, Switzerland)

DOI

EISSN

2076-0817

ISSN

2076-0817

Publication Date

July 2020

Volume

9

Issue

8

Start / End Page

E607

Related Subject Headings

  • 3207 Medical microbiology
  • 3204 Immunology
  • 3107 Microbiology
  • 1108 Medical Microbiology
  • 1107 Immunology