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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
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.
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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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