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Multiplex Immunofluorescence for Detection of Spatial Distributions of Infiltrating T Cells Within Different Regions of Hepatic Lobules During Liver Transplantation Rejection

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Abstract—

It remains unclear as to whether there are differences that exist in the types and functional status of immune cells within different areas of the liver lobules after rejection of liver transplantation. The composition of infiltrating T cells in liver allografts during liver transplantation rejection is indistinct and difficult to visualize within the same biopsy slide. In an attempt to rectify this problem, we applied multiplex immunofluorescent assays to assess the spatial distribution of various types of infiltrating T cells in different areas of the liver lobules after liver transplantation. In identical areas of the hepatic lobules, the percentage of CD4+ T, CD8+ T, and regulatory T (Treg) cells in the rejection group was greater than that observed in the non-rejection and normal groups. Within all three groups, the percentage of CD4+ T, CD8+ T, and Treg cells from the periportal to perivenous zones initially increased and then decreased. In the rejection group, the percentage of CD8+ T cells gradually increased from the periportal to perivenous zones, with maximal levels in the perivenous as compared with that in the transitional and periportal zones. In conclusion, levels of CD8+ T cells within different regions of liver lobules are closely related to levels of rejection after liver transplantation. Liver transplantation rejection may be linked with increases in CD8+ T cells within the perivenous zone. Although the regional percent of increase in CD4+ T cells may not reflect level of the rejection, the overall numbers of both of CD4+ and CD8+ T cells within different regions were closely related to rejection levels.

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Acknowledgements

The authors would like to thank the Key Laboratory of Transplantation immunity of Beijing for their technical support.

Funding

This work was supported by the National Natural Science Foundation of China (No. 81970562).

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Authors and Affiliations

  1. Liver Transplantation Center, Clinical Research Center for Pediatric Liver Transplantation, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China

    Shi-peng Li, Guang-peng Zhou, Jie Sun, Bin Cui, Hai-ming Zhang, Lin Wei, Li-ying Sun & Zhi-jun Zhu

  2. Clinical Research Center for Pediatric Liver, Transplantation of Capital Medical University, Beijing, 100050, China

    Shi-peng Li, Guang-peng Zhou, Jie Sun, Bin Cui, Hai-ming Zhang, Lin Wei, Li-ying Sun & Zhi-jun Zhu

  3. National Clinical Research Center for Digestive Diseases, Beijing, 100050, China

    Shi-peng Li, Guang-peng Zhou, Jie Sun, Bin Cui, Hai-ming Zhang, Lin Wei, Li-ying Sun & Zhi-jun Zhu

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  1. Shi-peng Li
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  2. Guang-peng Zhou
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  3. Jie Sun
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  4. Bin Cui
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  7. Li-ying Sun
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Contributions

Shi-peng Li and Zhi-jun Zhu contributed to the research design. Guang-peng Zhou, Jie Sun, and Bin Cui collected the clinical data; Shi-peng Li and Jie Sun performed multiplex immunofluorescent assays and immunocytochemistry. Hai-ming Zhang, Lin Wei, and Li-ying Sun contributed to the data management and statistical analyses. Shi-peng Li and Zhi-jun Zhu wrote the manuscript. Shi-peng Li and Guang-peng Zhou contributed equally to this work.

Corresponding authors

Correspondence to Li-ying Sun or Zhi-jun Zhu.

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The study protocol was approved by the ethics committee of Beijing Friendship Hospital, Capital Medical University, Beijing, China.

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Li, Sp., Zhou, Gp., Sun, J. et al. Multiplex Immunofluorescence for Detection of Spatial Distributions of Infiltrating T Cells Within Different Regions of Hepatic Lobules During Liver Transplantation Rejection. Inflammation 45, 651–664 (2022). https://doi.org/10.1007/s10753-021-01574-0

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  • DOI: https://doi.org/10.1007/s10753-021-01574-0

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