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Sirolimus Increases T-Cell Abundance in the Sun Exposed Skin of Kidney Transplant Recipients
BACKGROUND: Kidney transplant recipients (KTRs) receiving the mammalian target of rapamycin inhibitor sirolimus may display a reduced risk of skin cancer development compared to KTRs receiving calcineurin inhibitors. Despite studies investigating the effects of these 2 drug classes on T cells in pat...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498012/ https://www.ncbi.nlm.nih.gov/pubmed/28706974 http://dx.doi.org/10.1097/TXD.0000000000000694 |
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author | Burke, Michael Thomas Sambira Nahum, Lauren C. Isbel, Nicole M. Carroll, Robert P. Soyer, Hans Peter Francis, Ross Bridge, Jennifer Anne Hawley, Carmel Oliver, Kimberly Staatz, Christine E. Wells, James William |
author_facet | Burke, Michael Thomas Sambira Nahum, Lauren C. Isbel, Nicole M. Carroll, Robert P. Soyer, Hans Peter Francis, Ross Bridge, Jennifer Anne Hawley, Carmel Oliver, Kimberly Staatz, Christine E. Wells, James William |
author_sort | Burke, Michael Thomas |
collection | PubMed |
description | BACKGROUND: Kidney transplant recipients (KTRs) receiving the mammalian target of rapamycin inhibitor sirolimus may display a reduced risk of skin cancer development compared to KTRs receiving calcineurin inhibitors. Despite studies investigating the effects of these 2 drug classes on T cells in patient blood, the effect these drugs may have in patient skin is not yet known. METHODS: Fifteen patients with chronic kidney disease (not recipients of immunosuppressive drugs), and 30 KTRs (15 receiving a calcineurin inhibitor, and 15 receiving sirolimus) provided matched samples of blood, sun exposed (SE) and non-SE skin. The abundance of total CD8(+) and CD4(+) T cells, memory CD8(+) and CD4(+) T cells, and regulatory T (Treg) cells in each sample was then assessed by flow cytometry. RESULTS: Sirolimus treatment significantly increased absolute numbers of CD4(+) T cells, memory CD8(+)- and CD4(+) T cells, and Treg cells in SE skin versus paired samples of non-SE skin. No differences were found in the absolute number of any T cell subset in the blood. Correlation analysis revealed that the percentage of T cell subsets in the blood does not always accurately reflect the percentage of T-cell subsets in the skin of KTRs. Furthermore, sirolimus significantly disrupts the balance of memory CD4(+) T cells in the skin after chronic sun exposure. CONCLUSIONS: This study demonstrated that immunosuppressive drug class and sun exposure modify the abundance of multiple T-cell subsets in the skin of KTRs. Correlation analysis revealed that the prevalence of Treg cells in KTR blood does not accurately reflect the prevalence of Treg cells in KTR skin. |
format | Online Article Text |
id | pubmed-5498012 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-54980122017-07-13 Sirolimus Increases T-Cell Abundance in the Sun Exposed Skin of Kidney Transplant Recipients Burke, Michael Thomas Sambira Nahum, Lauren C. Isbel, Nicole M. Carroll, Robert P. Soyer, Hans Peter Francis, Ross Bridge, Jennifer Anne Hawley, Carmel Oliver, Kimberly Staatz, Christine E. Wells, James William Transplant Direct Kidney Transplantation BACKGROUND: Kidney transplant recipients (KTRs) receiving the mammalian target of rapamycin inhibitor sirolimus may display a reduced risk of skin cancer development compared to KTRs receiving calcineurin inhibitors. Despite studies investigating the effects of these 2 drug classes on T cells in patient blood, the effect these drugs may have in patient skin is not yet known. METHODS: Fifteen patients with chronic kidney disease (not recipients of immunosuppressive drugs), and 30 KTRs (15 receiving a calcineurin inhibitor, and 15 receiving sirolimus) provided matched samples of blood, sun exposed (SE) and non-SE skin. The abundance of total CD8(+) and CD4(+) T cells, memory CD8(+) and CD4(+) T cells, and regulatory T (Treg) cells in each sample was then assessed by flow cytometry. RESULTS: Sirolimus treatment significantly increased absolute numbers of CD4(+) T cells, memory CD8(+)- and CD4(+) T cells, and Treg cells in SE skin versus paired samples of non-SE skin. No differences were found in the absolute number of any T cell subset in the blood. Correlation analysis revealed that the percentage of T cell subsets in the blood does not always accurately reflect the percentage of T-cell subsets in the skin of KTRs. Furthermore, sirolimus significantly disrupts the balance of memory CD4(+) T cells in the skin after chronic sun exposure. CONCLUSIONS: This study demonstrated that immunosuppressive drug class and sun exposure modify the abundance of multiple T-cell subsets in the skin of KTRs. Correlation analysis revealed that the prevalence of Treg cells in KTR blood does not accurately reflect the prevalence of Treg cells in KTR skin. Lippincott Williams & Wilkins 2017-06-06 /pmc/articles/PMC5498012/ /pubmed/28706974 http://dx.doi.org/10.1097/TXD.0000000000000694 Text en Copyright © 2017 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Kidney Transplantation Burke, Michael Thomas Sambira Nahum, Lauren C. Isbel, Nicole M. Carroll, Robert P. Soyer, Hans Peter Francis, Ross Bridge, Jennifer Anne Hawley, Carmel Oliver, Kimberly Staatz, Christine E. Wells, James William Sirolimus Increases T-Cell Abundance in the Sun Exposed Skin of Kidney Transplant Recipients |
title | Sirolimus Increases T-Cell Abundance in the Sun Exposed Skin of Kidney Transplant Recipients |
title_full | Sirolimus Increases T-Cell Abundance in the Sun Exposed Skin of Kidney Transplant Recipients |
title_fullStr | Sirolimus Increases T-Cell Abundance in the Sun Exposed Skin of Kidney Transplant Recipients |
title_full_unstemmed | Sirolimus Increases T-Cell Abundance in the Sun Exposed Skin of Kidney Transplant Recipients |
title_short | Sirolimus Increases T-Cell Abundance in the Sun Exposed Skin of Kidney Transplant Recipients |
title_sort | sirolimus increases t-cell abundance in the sun exposed skin of kidney transplant recipients |
topic | Kidney Transplantation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498012/ https://www.ncbi.nlm.nih.gov/pubmed/28706974 http://dx.doi.org/10.1097/TXD.0000000000000694 |
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