Kidney Week

Abstract: FR-PO997

Kidney Transplantation in Mice Leads to Allograft-Restricted Activation and Maintenance of Allospecific Memory T Cells

Session Information

• Transplantation: Basic
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 2101 Transplantation: Basic

Authors

• Wang, Bo, Institute of Microbiology and Hygience, Faculty of Medicine, University of Freiburg, Freiburg, Germany

Bo Wang, MD, PhD

• Kupferschmid, Laurence, Institute of Microbiology and Hygience, Faculty of Medicine, University of Freiburg, Freiburg, Germany

Laurence Kupferschmid

• Arnold, Frederic, Institute of Microbiology and Hygience, Faculty of Medicine, University of Freiburg, Freiburg, Germany

Frederic Arnold, MD

• Liu, Xudong, Institute of Microbiology and Hygience, Faculty of Medicine, University of Freiburg, Freiburg, Germany

Xudong Liu

• -, Sagar, Department of Internal Medicine II, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany

Sagar -, PhD

• Schell, Christoph, Institute of Surgical Pathology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany

Christoph Schell, MD, PhD

• Tanriver, Yakup, Institute of Microbiology and Hygience, Faculty of Medicine, University of Freiburg, Freiburg, Germany

Yakup Tanriver, MD

Background

Pre-existing allospecific memory T cells are rapidly activated in response to allografts, expressing functions that mediate graft injury and failure, directly impacting patient survival. However, the early dynamics of their activation, graft infiltration, and effector functions remain largely unclear. Therefore, it is crucial to gain an in-depth understanding of their activation, migration, and effector functions during transplantation, including their ability to recruit other immune cells to drive allograft rejection.

Methods

To address those open questions, we infected recipient mice (wt) with OVA expressing Listeria monocytogenes (LM-OVA) to generate allospecific memory against OVA. Four weeks later, we transplanted kidneys from Act-mOVA transgenic mice, which express ovalbumin ubiquitously as an alloantigen. Then, we use fluorochrome-conjugated SIINFEKL: H2-Kb tetramer (SIIN-tet) to follow the dynamics of the endogenous CD8 T cells response against OVA after kidney transplantation. Finally, single cell RNA sequencing was used to obtain a comprehensive understanding of the immune cell landscape within allogenic kidney grafts on day 14.

Results

We show that in contrast to pathogen-activated memory T cells allospecific memory T cells are not activated in secondary lymphoid organs but rather directly in the allograft, where they are a maintained by forming a stem-like population, proliferate and differentiate in response to their cognate antigen. This interaction leads to the recruitment and activation of various immune subsets, ultimately resulting in allograft rejection. In addition, the scRNA-seq data expose a complex composition of myeloid and lymphoid immune cell subsets and pathogenic transcriptional states in the kidney allograft, which is orchestrated by the T cell memory response.

Conclusion

Allospecific memory T cells have a unique response pattern, which will help to devise new strategies to prevent and treat allograft rejection that is mediated by memory T cells