Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse

Tian, Guangyao; Li, Mingqian; Lv, Guoyue

doi:10.3389/fimmu.2021.778559

Cited by 13 publications

(8 citation statements)

References 149 publications

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“…Then, we simultaneously analyzed transcriptomes and TCR sequences at the single-cell level to investigate the correlation between Pdcd1 expression and clonal expansion in endogenous alloreactive T cells (fig. S3A) ( 28 ). CD8 + T cells in Allografts, Allo-spleens, and Iso-spleens were combined and then divided into three clusters according to their clonal expansion.…”

Section: Resultsmentioning

confidence: 99%

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

Cui,

Xu,

et al. 2024

Sci. Immunol.

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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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Section: Resultsmentioning

confidence: 99%

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

Cui,

Xu,

et al. 2024

Sci. Immunol.

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“…Clonal expansion and loss of TCR diversity have been linked to alloreactive T cells ( 16 ). Therefore, we postulated that recipient T RM cells would have higher TCR clonality than donor T RM cells.…”

Section: Resultsmentioning

confidence: 99%

Virus-specific TRM cells of both donor and recipient origin reside in human kidney transplants

Hullegie-Peelen,

Tejeda Mora,

Hesselink

et al. 2023

JCI Insight

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Tissue-resident lymphocytes (TRLs) are critical for local protection against viral pathogens in peripheral tissue. However, it is unclear if TRLs perform a similar role in transplanted organs under chronic immunosuppressed conditions. In this study, we aimed to characterize the TRL compartment in human kidney transplant nephrectomies and examine its potential role in antiviral immunity. The TRL compartment of kidney transplants contained diverse innate, innate-like, and adaptive TRL populations expressing the canonical residency markers CD69, CD103, and CD49a. Chimerism of donor and recipient cells was present in 43% of kidney transplants and occurred in all TRL subpopulations. Paired single-cell transcriptome and T cell receptor (TCR) sequencing showed that donor and recipient tissue–resident memory T (T RM ) cells exhibit striking similarities in their transcriptomic profiles and share numerous TCR clonotypes predicted to target viral pathogens. Virus dextramer staining further confirmed that CD8 T RM cells of both donor and recipient origin express TCRs with specificities against common viruses, including CMV, EBV, BK polyomavirus, and influenza A. Overall, the study results demonstrate that a diverse population of TRLs resides in kidney transplants and offer compelling evidence that T RM cells of both donor and recipient origin reside within this TRL population and may contribute to local protection against viral pathogens.

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“…Therefore, standard tools for identifying variants (variations in nucleotides at a given position compared with the human reference genome) in the DNA-seq data can also be applied here. 15 Bulk RNA-seq contains a plethora of other information, including estimating T-and B-cell receptor (TCR and BCR) repertoire, 16,17 and the role of noncoding RNAs such as micro-RNA (miRNA) 18 and circular RNAs. 19,20 Unlike bulk RNA-seq, sc/snRNA-seq provides data at cellular resolution.…”

Section: Potential End Points For Rna-seq Experimentsmentioning

confidence: 99%

Standardization and Interpretation of RNA-sequencing for Transplantation

et al. 2023

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RNA-sequencing (RNA-seq) is a technique to determine the order of nucleotides in an RNA segment. Modern sequencing platforms simultaneously sequence millions of RNA molecules. Advances in bioinformatics have allowed us to collect, store, analyze, and disseminate data from RNA-seq experiments and decipher biological insights from large sequencing datasets. Although bulk RNA-seq has significantly advanced our understanding of tissue-specific gene expression and regulation, recent advances in single-cell RNA-seq have allowed such information to be mapped to individual cells, thus remarkably enhancing our insight into discrete cellular functions within a biospecimen. These different RNA-seq experimental approaches require specialized computational tools. Herein, we will first review the RNA-seq experimental workflow, discuss the common terminologies used in RNA-seq, and suggest approaches for standardization across multiple studies. Next, we will provide an up-to-date appraisal of the applications of bulk RNA-seq and single-cell/nucleus RNA-seq in preclinical and clinical research on kidney transplantation, as well as typical bioinformatic workflows utilized in such analysis. Lastly, we will deliberate on the limitations of this technology in transplantation research and briefly summarize newer technologies that could be combined with RNA-seq to permit more powerful dissections of biological functions. Because each step in RNA-seq workflow has numerous variations and could potentially impact the results, as conscientious citizens of the research community, we must strive to continuously modernize our analytical pipelines and exhaustively report their technical details.

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Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse

Cited by 13 publications

References 149 publications

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

Virus-specific TRM cells of both donor and recipient origin reside in human kidney transplants

Standardization and Interpretation of RNA-sequencing for Transplantation

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