Deep phenotyping of T cell populations under long‐term treatment of tacrolimus and rapamycin in patients receiving renal transplantations by mass cytometry

Abstract Tacrolimus (FK506) and rapamycin (RAPA) are widely used to maintain long‐term immunosuppression after organ transplantation. However, the impact of accumulative drug administration on the recipients’ immune systems remains unclear. We investigated the impact of 3‐year FK506 or RAPA treatmen...

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Autores principales:	Yiyang Li, Huimin An, Chuan Shen, Boqian Wang, Ting Zhang, Yifan Hong, Hui Jiang, Peijun Zhou, Xianting Ding
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	immune system mass cytometry rapamycin renal transplantation tacrolimus Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/66b51bd9d55845f2b66e44d42a9f19df
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spelling	oai:doaj.org-article:66b51bd9d55845f2b66e44d42a9f19df2021-11-30T07:25:38ZDeep phenotyping of T cell populations under long‐term treatment of tacrolimus and rapamycin in patients receiving renal transplantations by mass cytometry2001-132610.1002/ctm2.629https://doaj.org/article/66b51bd9d55845f2b66e44d42a9f19df2021-11-01T00:00:00Zhttps://doi.org/10.1002/ctm2.629https://doaj.org/toc/2001-1326Abstract Tacrolimus (FK506) and rapamycin (RAPA) are widely used to maintain long‐term immunosuppression after organ transplantation. However, the impact of accumulative drug administration on the recipients’ immune systems remains unclear. We investigated the impact of 3‐year FK506 or RAPA treatment after renal transplantation on the human immune systems. A discovery cohort of 30 patients was first recruited, and we discovered two distinctive T lineage suppressive regulatory patterns induced by chronic treatment of FK506 and RAPA. The increased percentage of senescent CD8+CD57+ T lineages and less responsive T cell receptor (TCR) pathway in the FK506 group indicate better graft acceptance. Meanwhile, percentages of regulatory T cells (Tregs) and expression of CTLA‐4 were both up to two‐fold higher in the RAPA group, suggesting the inconsistent reactivation potential of the FK506 and RAPA groups when an anti‐tumour or anti‐infection immune response is concerned. Additionally, up‐regulation of phosphorylated signaling proteins in T lineages after in vitro CD3/CD28 stimulation suggested more sensitive TCR‐signaling pathways reserved in the RAPA group. An independent validation cohort of 100 renal transplantation patients was further investigated for the hypothesis that long‐term RAPA administration mitigates the development of tumours and infections during long‐term intake of immunosuppressants. Our results indicate that RAPA administration indeed results in less clinical oncogenesis and infection. The deep phenotyping of T‐cell lineages, as educated by the long‐term treatment of different immunosuppressants, provides new evidence for personalized precision medicine after renal transplantations.Yiyang LiHuimin AnChuan ShenBoqian WangTing ZhangYifan HongHui JiangPeijun ZhouXianting DingWileyarticleimmune systemmass cytometryrapamycinrenal transplantationtacrolimusMedicine (General)R5-920ENClinical and Translational Medicine, Vol 11, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	immune system mass cytometry rapamycin renal transplantation tacrolimus Medicine (General) R5-920
spellingShingle	immune system mass cytometry rapamycin renal transplantation tacrolimus Medicine (General) R5-920 Yiyang Li Huimin An Chuan Shen Boqian Wang Ting Zhang Yifan Hong Hui Jiang Peijun Zhou Xianting Ding Deep phenotyping of T cell populations under long‐term treatment of tacrolimus and rapamycin in patients receiving renal transplantations by mass cytometry
description	Abstract Tacrolimus (FK506) and rapamycin (RAPA) are widely used to maintain long‐term immunosuppression after organ transplantation. However, the impact of accumulative drug administration on the recipients’ immune systems remains unclear. We investigated the impact of 3‐year FK506 or RAPA treatment after renal transplantation on the human immune systems. A discovery cohort of 30 patients was first recruited, and we discovered two distinctive T lineage suppressive regulatory patterns induced by chronic treatment of FK506 and RAPA. The increased percentage of senescent CD8+CD57+ T lineages and less responsive T cell receptor (TCR) pathway in the FK506 group indicate better graft acceptance. Meanwhile, percentages of regulatory T cells (Tregs) and expression of CTLA‐4 were both up to two‐fold higher in the RAPA group, suggesting the inconsistent reactivation potential of the FK506 and RAPA groups when an anti‐tumour or anti‐infection immune response is concerned. Additionally, up‐regulation of phosphorylated signaling proteins in T lineages after in vitro CD3/CD28 stimulation suggested more sensitive TCR‐signaling pathways reserved in the RAPA group. An independent validation cohort of 100 renal transplantation patients was further investigated for the hypothesis that long‐term RAPA administration mitigates the development of tumours and infections during long‐term intake of immunosuppressants. Our results indicate that RAPA administration indeed results in less clinical oncogenesis and infection. The deep phenotyping of T‐cell lineages, as educated by the long‐term treatment of different immunosuppressants, provides new evidence for personalized precision medicine after renal transplantations.
format	article
author	Yiyang Li Huimin An Chuan Shen Boqian Wang Ting Zhang Yifan Hong Hui Jiang Peijun Zhou Xianting Ding
author_facet	Yiyang Li Huimin An Chuan Shen Boqian Wang Ting Zhang Yifan Hong Hui Jiang Peijun Zhou Xianting Ding
author_sort	Yiyang Li
title	Deep phenotyping of T cell populations under long‐term treatment of tacrolimus and rapamycin in patients receiving renal transplantations by mass cytometry
title_short	Deep phenotyping of T cell populations under long‐term treatment of tacrolimus and rapamycin in patients receiving renal transplantations by mass cytometry
title_full	Deep phenotyping of T cell populations under long‐term treatment of tacrolimus and rapamycin in patients receiving renal transplantations by mass cytometry
title_fullStr	Deep phenotyping of T cell populations under long‐term treatment of tacrolimus and rapamycin in patients receiving renal transplantations by mass cytometry
title_full_unstemmed	Deep phenotyping of T cell populations under long‐term treatment of tacrolimus and rapamycin in patients receiving renal transplantations by mass cytometry
title_sort	deep phenotyping of t cell populations under long‐term treatment of tacrolimus and rapamycin in patients receiving renal transplantations by mass cytometry
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/66b51bd9d55845f2b66e44d42a9f19df
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Deep phenotyping of T cell populations under long‐term treatment of tacrolimus and rapamycin in patients receiving renal transplantations by mass cytometry

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