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Anti‐thymocyte globulin‐mediated immunosenescent alterations of T cells in kidney transplant patients
OBJECTIVES: Kidney transplant (KT) is the most effective treatment for end‐stage renal disease. The immunosuppressant anti‐thymocyte globulin (ATG) has been applied for induction therapy to reduce the risk of acute transplant rejection for patients at high immunological risk. Despite its putative ro...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686013/ https://www.ncbi.nlm.nih.gov/pubmed/36439636 http://dx.doi.org/10.1002/cti2.1431 |
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author | Lee, Ga Hye Lee, Jee Youn Jang, Jiyeon Kang, Yeon Jun Choi, Seung Ah Kim, Hyeon Chang Park, Sungha Kim, Myoung Soo Lee, Won‐Woo |
author_facet | Lee, Ga Hye Lee, Jee Youn Jang, Jiyeon Kang, Yeon Jun Choi, Seung Ah Kim, Hyeon Chang Park, Sungha Kim, Myoung Soo Lee, Won‐Woo |
author_sort | Lee, Ga Hye |
collection | PubMed |
description | OBJECTIVES: Kidney transplant (KT) is the most effective treatment for end‐stage renal disease. The immunosuppressant anti‐thymocyte globulin (ATG) has been applied for induction therapy to reduce the risk of acute transplant rejection for patients at high immunological risk. Despite its putative role in replicative stress during immune reconstitution, the effects of ATG on T‐cell immunosenescent changes remain to be understood. METHODS: Phenotypic and functional features of senescent T cells were examined by flow cytometry in 116 healthy controls (HC) and 95 KT patients for comparative analysis according to ATG treatment and CMV reactivation. The TCR repertoire was analysed in peripheral blood mononuclear cells (PBMCs) of KT patients. RESULTS: T cells of KT patients treated with ATG (ATG(+)) show typical immunosenescent features, accumulation of CD28(−), CD85j(+) or CD57(+) T cells, and imbalance of functional T‐cell subsets, compared with untreated KT patients (ATG(−)). Plasma IL‐15 and CMV‐IgG levels were higher in KT patients than in HCs, and the IL‐15 level positively correlated with the frequency of CD28(−) T cells in KT patients. ATG(+) patients had a higher prevalence of CMV reactivation, which is associated with an increased frequency of CD28(−) T cells. As a result, ATG(+) patients had expanded CMV‐specific T cells and decreased TCR diversity. However, proliferation, cytokine‐producing capacity and polyfunctionality of T cells were preserved in ATG(+) patients. CONCLUSION: Our findings suggest that ATG treatment contributes to the accumulation of senescent T cells, which may have lifelong clinical implications in KT patients. Thus, these patients require long‐term and comprehensive immune monitoring. |
format | Online Article Text |
id | pubmed-9686013 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96860132022-11-25 Anti‐thymocyte globulin‐mediated immunosenescent alterations of T cells in kidney transplant patients Lee, Ga Hye Lee, Jee Youn Jang, Jiyeon Kang, Yeon Jun Choi, Seung Ah Kim, Hyeon Chang Park, Sungha Kim, Myoung Soo Lee, Won‐Woo Clin Transl Immunology Original Articles OBJECTIVES: Kidney transplant (KT) is the most effective treatment for end‐stage renal disease. The immunosuppressant anti‐thymocyte globulin (ATG) has been applied for induction therapy to reduce the risk of acute transplant rejection for patients at high immunological risk. Despite its putative role in replicative stress during immune reconstitution, the effects of ATG on T‐cell immunosenescent changes remain to be understood. METHODS: Phenotypic and functional features of senescent T cells were examined by flow cytometry in 116 healthy controls (HC) and 95 KT patients for comparative analysis according to ATG treatment and CMV reactivation. The TCR repertoire was analysed in peripheral blood mononuclear cells (PBMCs) of KT patients. RESULTS: T cells of KT patients treated with ATG (ATG(+)) show typical immunosenescent features, accumulation of CD28(−), CD85j(+) or CD57(+) T cells, and imbalance of functional T‐cell subsets, compared with untreated KT patients (ATG(−)). Plasma IL‐15 and CMV‐IgG levels were higher in KT patients than in HCs, and the IL‐15 level positively correlated with the frequency of CD28(−) T cells in KT patients. ATG(+) patients had a higher prevalence of CMV reactivation, which is associated with an increased frequency of CD28(−) T cells. As a result, ATG(+) patients had expanded CMV‐specific T cells and decreased TCR diversity. However, proliferation, cytokine‐producing capacity and polyfunctionality of T cells were preserved in ATG(+) patients. CONCLUSION: Our findings suggest that ATG treatment contributes to the accumulation of senescent T cells, which may have lifelong clinical implications in KT patients. Thus, these patients require long‐term and comprehensive immune monitoring. John Wiley and Sons Inc. 2022-11-24 /pmc/articles/PMC9686013/ /pubmed/36439636 http://dx.doi.org/10.1002/cti2.1431 Text en © 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd, on behalf of Australian and New Zealand Society for Immunology, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Lee, Ga Hye Lee, Jee Youn Jang, Jiyeon Kang, Yeon Jun Choi, Seung Ah Kim, Hyeon Chang Park, Sungha Kim, Myoung Soo Lee, Won‐Woo Anti‐thymocyte globulin‐mediated immunosenescent alterations of T cells in kidney transplant patients |
title | Anti‐thymocyte globulin‐mediated immunosenescent alterations of T cells in kidney transplant patients |
title_full | Anti‐thymocyte globulin‐mediated immunosenescent alterations of T cells in kidney transplant patients |
title_fullStr | Anti‐thymocyte globulin‐mediated immunosenescent alterations of T cells in kidney transplant patients |
title_full_unstemmed | Anti‐thymocyte globulin‐mediated immunosenescent alterations of T cells in kidney transplant patients |
title_short | Anti‐thymocyte globulin‐mediated immunosenescent alterations of T cells in kidney transplant patients |
title_sort | anti‐thymocyte globulin‐mediated immunosenescent alterations of t cells in kidney transplant patients |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686013/ https://www.ncbi.nlm.nih.gov/pubmed/36439636 http://dx.doi.org/10.1002/cti2.1431 |
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