2. Academic Validation
  3. Targeted depletion of PD-1-expressing cells induces immune tolerance through peripheral clonal deletion

Targeted depletion of PD-1-expressing cells induces immune tolerance through peripheral clonal deletion

  • Sci Immunol. 2024 Apr 26;9(94):eadh0085. doi: 10.1126/sciimmunol.adh0085.
Jikai Cui 1 2 3,  Heng Xu 1,  Jizhang Yu 1 2 3 4,  Shuan Ran 1 2 3,  Xi Zhang 1 2 3,  Yuan Li 1 2 3,  Zhang Chen 1 2 3,  Yuqing Niu 1 2 3,  Song Wang 1 2 3,  Weicong Ye 1 2 3,  Wenhao Chen 5,  Jie Wu 1 2 3 4 6,  Jiahong Xia 1 2 3 4 6
Affiliations

Affiliations

  • 1 Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China.
  • 4 Center for Translational Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 5 Immunobiology and Transplant Science Center, Department of Surgery, Houston Methodist Research Institute and Institute for Academic Medicine, Houston Methodist Hospital, Houston, TX, USA.
  • 6 Institute of Translational Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
PMID: 38669317 DOI: 10.1126/sciimmunol.adh0085
Abstract

Thymic negative selection of the T cell receptor (TCR) repertoire is essential for establishing self-tolerance and acquired allograft tolerance following organ transplantation. However, it is unclear whether and how peripheral clonal deletion of alloreactive T cells induces transplantation tolerance. Here, we establish that programmed cell death protein 1 (PD-1) is a hallmark of alloreactive T cells and is associated with clonal expansion after alloantigen encounter. Moreover, we found that diphtheria toxin receptor (DTR)-mediated ablation of PD-1+ cells reshaped the TCR repertoire through peripheral clonal deletion of alloreactive T cells and promoted tolerance in mouse transplantation models. In addition, by using PD-1-specific depleting Antibodies, we found that antibody-mediated depletion of PD-1+ cells prevented heart transplant rejection and the development of experimental autoimmune encephalomyelitis (EAE) in humanized PD-1 mice. Thus, these data suggest that PD-1 is an attractive target for peripheral clonal deletion and induction of immune tolerance.

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