期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 19, 页码 -出版社
MDPI
DOI: 10.3390/ijms241914463
关键词
donor-reactive; alloreactive; T lymphocyte; hyporesponsive; flow cytometry; clustering; single cell; expression profiling
After kidney transplantation, recipient T cells develop low responsiveness to donor-specific antigens over time. Apoptosis was identified as a possible underlying mechanism. This study investigated the genetic and receptor profiles of individual alloreactive T cells from kidney transplant recipients using single-cell RNA sequencing. The findings suggest that post-transplantation, donor-reactive CD4+ T cell clones preferentially undergo apoptosis in stable kidney transplant recipients.
After kidney transplantation (KT), donor-specific hyporesponsiveness (DSH) of recipient T cells develops over time. Recently, apoptosis was identified as a possible underlying mechanism. In this study, both transcriptomic profiles and complete V(D)J variable regions of TR transcripts from individual alloreactive T cells of kidney transplant recipients were determined with single-cell RNA sequencing. Alloreactive T cells were identified by CD137 expression after stimulation of peripheral blood mononuclear cells obtained from KT recipients (N = 7) prior to and 3-5 years after transplantation with cells of their donor or a third party control. The alloreactive T cells were sorted, sequenced and the transcriptome and T cell receptor profiles were analyzed using unsupervised clustering. Alloreactive T cells retain a highly polyclonal T Cell Receptor Alpha/Beta repertoire over time. Post transplantation, donor-reactive CD4+ T cells had a specific downregulation of genes involved in T cell cytokine-mediated pathways and apoptosis. The CD8+ donor-reactive T cell profile did not change significantly over time. Single-cell expression profiling shows that activated and pro-apoptotic donor-reactive CD4+ T cell clones are preferentially lost after transplantation in stable kidney transplant recipients.
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