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. 2023 Jul 20;12(14):4786.
doi: 10.3390/jcm12144786.

Impact of T Lymphocytes Isolated from Liver Perfusate of Deceased Brain Donors on Kidney Transplantation: Preliminary Evidence and Future Directions

Duilio Pagano  1 , Ester Badami  2   3 , Giovanni Zito  2 , Pier Giulio Conaldi  2 , Ivan Vella  1 , Barbara Buscemi  4 , Giandomenico Amico  3 , Rosalia Busà  2 , Paola Salis  4 , Sergio Li Petri  1 , Fabrizio di Francesco  1 , Sergio Calamia  1 , Pasquale Bonsignore  1 , Alessandro Tropea  1 , Caterina Accardo  1 , Salvatore Piazza  1 , Salvatore Gruttadauria  1   5
Affiliations

Impact of T Lymphocytes Isolated from Liver Perfusate of Deceased Brain Donors on Kidney Transplantation: Preliminary Evidence and Future Directions

Duilio Pagano et al. J Clin Med. .

Abstract

Background: Ischemia/reperfusion injury (IRI), acute rejection (AR), and delayed graft function (DGF) might occur as major complications following kidney transplantation. Thus, the identification of biomarkers for the IRI, AR, and/or DGF development becomes crucial as it may help to guide post-transplant management. Natural killer (NK) cells, hepatic interstitial T-lymphocytes (T-Li), and NK-T cells are crucial in both innate and adaptive immunity after abdominal solid organ transplantation. Hence, the aim of this study was to evaluate the impact of the immune system after graft reperfusion during KT in adults in order to identify predictive biomarkers.

Methods: The NK, T-Li, and NK-T phenotypes and concentrations were retrospectively analyzed in a consecutive series of liver perfusates obtained after organ procurement flushing the abdominal cavity recovered from deceased brain donors (DBDs). Their percentage was compared with the renal transplant recipients' characteristics with kidneys taken from the same DCDs. The hepatic perfusate cells were purified by density gradient centrifugation. Flow cytometric investigation was used to determine their phenotype with the following immunological markers in order to determine the relative percentage of T-Li, NK-T, and NK cells: CD3, CD4, CD8, and CD56.

Results: 42 DBDs' liver perfusates were analyzed. The related clinical outcomes of kidney transplant recipients from 2010 to 2020 performed at our Institute were evaluated. Time in days of delayed functional recovery of transplanted kidneys (DGF) (p = 0.02) and the onset of secondary infection from a cytomegalovirus (p = 0.03) were significantly associated with the T-Li percentage. An increased relative risk (HR) of organ survival was significantly associated with the percent cell concentration of T-Li and time to DGF, on COX analysis, were (HR = 1.038, p = 0.04; and HR = 1.029, p = 0.01, respectively). None relevant clinical outcomes in kidney transplant patients were associated with the specificity of the NK and NK-T cell proportions.

Conclusions: A new potential role of T-Li cells was detected in the context of hepatic perfusate from DBDs. It could detect potential impacts in organ allocation, surgical procuring techniques, and in the analysis of IRI pathophysiological events.

Keywords: T lymphocytes; deceased brain donors; hepatic perfusate; kidney transplantation.

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Conflict of interest statement

The authors declare no competing interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Figures

Figure 1
Figure 1
Phenotype of T cells in liver perfusate. CD8+ cytotoxic T lymphocytes were highly represented in the back-table fraction of the liver perfusate of matched donors and significantly more abundant compared to CD4+ T cells (**** p < 0.0001).
Figure 2
Figure 2
Linear regression analysis fit plotting percentage of T-cells and EGL-DRI score. Increasing the percentage of T cells (T-Li) by one reduces the EGL-DRI by 0.05977 (p-value = 0.0057).
See this image and copyright information in PMC

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