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<p>Therapeutic application of ex vivo expanded regulatory T cells is a promising approach to prolong allograft survival. In this work we performed a detailed characterization of a preclinical heterogenous antigen specific T enriched regulatory cell line (ASTRL) expanded ex vivo from PBMC of stable kidney transplant recipients. We used three different approaches: scRNA-seq, flow cytometry and mass cytometry, to compare pre-expansion PBMC to post-expansion ASTRL. Results show the CD4<sup>+</sup> T cell compartment in ASTRL clonally expanded in response to donor antigen stimulation and showed decreased TCR diversity. ASTRL CD4<sup>+</sup> T cells demonstrated a Treg associated transcriptome with upregulated CD39 and TIGIT together with other classical Treg genes like IL2RA, IKZF4, TNFRSF9, CXCR6, DUSP10 and HLA-DRA. Comparison of differentially expressed genes (DEGs) in ASTRL with classical Treg gene signatures showed strong overlap of genes associated with both peripheral and uterine Tregs together with a Th2-like Treg transcriptomic profile. In conclusion the CD4<sup>+</sup> T cell compartment of ASTRL acquire a regulatory T cell transcriptomic profile in response to donor antigen specific stimulation. This suggests a promising approach towards the development of a regulatory cell therapy in organ transplantation.</p>

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Single-cell and multi-omic characterization of ex vivo expanded ASTRLs from stable kidney transplant recipients reveals a regulatory T cell phenotype

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月14日

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  • Sudipta Tripathi,
  • Amélie M. Julé,
  • Zhu Zhuo,
  • Brittany L. Schreiber,
  • Paloma L. Martin-Moreno,
  • Shannan Ho Sui,
  • Ana Maria Waaga-Gasser,
  • Anil Chandraker

摘要

Therapeutic application of ex vivo expanded regulatory T cells is a promising approach to prolong allograft survival. In this work we performed a detailed characterization of a preclinical heterogenous antigen specific T enriched regulatory cell line (ASTRL) expanded ex vivo from PBMC of stable kidney transplant recipients. We used three different approaches: scRNA-seq, flow cytometry and mass cytometry, to compare pre-expansion PBMC to post-expansion ASTRL. Results show the CD4+ T cell compartment in ASTRL clonally expanded in response to donor antigen stimulation and showed decreased TCR diversity. ASTRL CD4+ T cells demonstrated a Treg associated transcriptome with upregulated CD39 and TIGIT together with other classical Treg genes like IL2RA, IKZF4, TNFRSF9, CXCR6, DUSP10 and HLA-DRA. Comparison of differentially expressed genes (DEGs) in ASTRL with classical Treg gene signatures showed strong overlap of genes associated with both peripheral and uterine Tregs together with a Th2-like Treg transcriptomic profile. In conclusion the CD4+ T cell compartment of ASTRL acquire a regulatory T cell transcriptomic profile in response to donor antigen specific stimulation. This suggests a promising approach towards the development of a regulatory cell therapy in organ transplantation.