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Expansion of CD45RA(−)FOXP3(++) regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation

OBJECTIVES: Simultaneous transplantation of a solid organ and bone marrow from the same donor is a possible means of achieving transplant tolerance. Here, we attempted to identify biomarkers that indicate transplant tolerance for discontinuation of immunosuppressants in combined kidney and bone marr...

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Autores principales: Kwon, Yeongbeen, Lee, Kyo Won, Kim, You Min, Park, Hyojun, Jung, Min Kyung, Choi, Young Joon, Son, Jin Kyung, Hong, JuHee, Park, Su‐Hyung, Kwon, Ghee Young, Yoo, Heejin, Kim, Kyunga, Kim, Sung Joo, Park, Jae Berm, Shin, Eui‐Cheol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353318/
https://www.ncbi.nlm.nih.gov/pubmed/34401148
http://dx.doi.org/10.1002/cti2.1325
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author Kwon, Yeongbeen
Lee, Kyo Won
Kim, You Min
Park, Hyojun
Jung, Min Kyung
Choi, Young Joon
Son, Jin Kyung
Hong, JuHee
Park, Su‐Hyung
Kwon, Ghee Young
Yoo, Heejin
Kim, Kyunga
Kim, Sung Joo
Park, Jae Berm
Shin, Eui‐Cheol
author_facet Kwon, Yeongbeen
Lee, Kyo Won
Kim, You Min
Park, Hyojun
Jung, Min Kyung
Choi, Young Joon
Son, Jin Kyung
Hong, JuHee
Park, Su‐Hyung
Kwon, Ghee Young
Yoo, Heejin
Kim, Kyunga
Kim, Sung Joo
Park, Jae Berm
Shin, Eui‐Cheol
author_sort Kwon, Yeongbeen
collection PubMed
description OBJECTIVES: Simultaneous transplantation of a solid organ and bone marrow from the same donor is a possible means of achieving transplant tolerance. Here, we attempted to identify biomarkers that indicate transplant tolerance for discontinuation of immunosuppressants in combined kidney and bone marrow transplantation (CKBMT). METHODS: Conventional kidney transplant (KT) recipients (n = 20) and CKBMT recipients (n = 6) were included in this study. We examined various immunological parameters by flow cytometry using peripheral blood mononuclear cells (PBMCs), including the frequency and phenotype of regulatory T (Treg) cell subpopulations. We also examined the suppressive activity of the Treg cell population in the setting of mixed lymphocyte reaction (MLR) with or without Treg cell depletion. RESULTS: Among six CKBMT recipients, three successfully discontinued immunosuppressants (tolerant group) and three could not (non‐tolerant group). The CD45RA(−)FOXP3(++) Treg cell subpopulation was expanded in CKBMT recipients compared to conventional kidney transplant patients, and this was more obvious in the tolerant group than the non‐tolerant group. In addition, high suppressive activity of the Treg cell population was observed in the tolerant group. The ratio of CD45RA(−)FOXP3(++) Treg cells to CD45RA(−)FOXP3(+) cells indicated good discrimination between the tolerant and non‐tolerant groups. CONCLUSION: Thus, our findings propose a biomarker that can distinguish CKBMT patients who achieve transplant tolerance and are eligible for discontinuation of immunosuppressants and may provide insight into tolerance mechanisms in CKBMT.
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spelling pubmed-83533182021-08-15 Expansion of CD45RA(−)FOXP3(++) regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation Kwon, Yeongbeen Lee, Kyo Won Kim, You Min Park, Hyojun Jung, Min Kyung Choi, Young Joon Son, Jin Kyung Hong, JuHee Park, Su‐Hyung Kwon, Ghee Young Yoo, Heejin Kim, Kyunga Kim, Sung Joo Park, Jae Berm Shin, Eui‐Cheol Clin Transl Immunology Original Articles OBJECTIVES: Simultaneous transplantation of a solid organ and bone marrow from the same donor is a possible means of achieving transplant tolerance. Here, we attempted to identify biomarkers that indicate transplant tolerance for discontinuation of immunosuppressants in combined kidney and bone marrow transplantation (CKBMT). METHODS: Conventional kidney transplant (KT) recipients (n = 20) and CKBMT recipients (n = 6) were included in this study. We examined various immunological parameters by flow cytometry using peripheral blood mononuclear cells (PBMCs), including the frequency and phenotype of regulatory T (Treg) cell subpopulations. We also examined the suppressive activity of the Treg cell population in the setting of mixed lymphocyte reaction (MLR) with or without Treg cell depletion. RESULTS: Among six CKBMT recipients, three successfully discontinued immunosuppressants (tolerant group) and three could not (non‐tolerant group). The CD45RA(−)FOXP3(++) Treg cell subpopulation was expanded in CKBMT recipients compared to conventional kidney transplant patients, and this was more obvious in the tolerant group than the non‐tolerant group. In addition, high suppressive activity of the Treg cell population was observed in the tolerant group. The ratio of CD45RA(−)FOXP3(++) Treg cells to CD45RA(−)FOXP3(+) cells indicated good discrimination between the tolerant and non‐tolerant groups. CONCLUSION: Thus, our findings propose a biomarker that can distinguish CKBMT patients who achieve transplant tolerance and are eligible for discontinuation of immunosuppressants and may provide insight into tolerance mechanisms in CKBMT. John Wiley and Sons Inc. 2021-08-09 /pmc/articles/PMC8353318/ /pubmed/34401148 http://dx.doi.org/10.1002/cti2.1325 Text en © 2021 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/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Kwon, Yeongbeen
Lee, Kyo Won
Kim, You Min
Park, Hyojun
Jung, Min Kyung
Choi, Young Joon
Son, Jin Kyung
Hong, JuHee
Park, Su‐Hyung
Kwon, Ghee Young
Yoo, Heejin
Kim, Kyunga
Kim, Sung Joo
Park, Jae Berm
Shin, Eui‐Cheol
Expansion of CD45RA(−)FOXP3(++) regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation
title Expansion of CD45RA(−)FOXP3(++) regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation
title_full Expansion of CD45RA(−)FOXP3(++) regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation
title_fullStr Expansion of CD45RA(−)FOXP3(++) regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation
title_full_unstemmed Expansion of CD45RA(−)FOXP3(++) regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation
title_short Expansion of CD45RA(−)FOXP3(++) regulatory T cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation
title_sort expansion of cd45ra(−)foxp3(++) regulatory t cells is associated with immune tolerance in patients with combined kidney and bone marrow transplantation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353318/
https://www.ncbi.nlm.nih.gov/pubmed/34401148
http://dx.doi.org/10.1002/cti2.1325
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