IL-10 and IL-4 in Skin Allograft Survival Induced by T-Cell Depletion plus Deoxyspergualin
The mechanisms mediating T-cell depletion plus 15-deoxyspergualin (DSG)-induced prolonged allograft survival or tolerance are uncertain. The purpose of this study is to evaluate the role of IL-4 and IL-10 in prolonged allograft survival induced by T-cell depletion plus DSG. MHC mismatched skin allog...
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doaj-22d85b94a99d45e8b8295e1751894b1d2020-11-25T02:59:52ZengSAGE PublishingCell Transplantation0963-68971555-38922008-06-011710.3727/096368908786092748IL-10 and IL-4 in Skin Allograft Survival Induced by T-Cell Depletion plus DeoxyspergualinClement Asiedu0Patricio Andrades1Peter D. Ray2James F. George3Judith M. Thomas4Division of Transplant Immunology, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USADivision of Plastic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USADivision of Plastic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USADivision of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USADivision of Transplant Immunology, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USAThe mechanisms mediating T-cell depletion plus 15-deoxyspergualin (DSG)-induced prolonged allograft survival or tolerance are uncertain. The purpose of this study is to evaluate the role of IL-4 and IL-10 in prolonged allograft survival induced by T-cell depletion plus DSG. MHC mismatched skin allograft transplantation was performed, using wild-type and three separate knockout (i.e., IL-4–/–, Stat6–/-, or IL-10–/–) mice as recipients. Induction therapy consisted of T-cell depletion and or brief course of DSG. The data demonstrate that monotherapy with T-cell-depleting mAbs or DSG prolonged skin allograft survival, compared to controls, in wild-type Balb/c recipients [median survival time (MST) = 25 and 21 vs. 10 days, p < 0.007]. T-cell depletion plus DSG further augmented skin allograft survival in wild-type animals relative to monotherapy (MST = 35 days vs. 25 and 21 days, p < 0.006 vs. mAbs or DSG only), and was equally effective in IL-4–/– and Stat6–/– recipients. In contrast, combined therapy was no better than monotherapy in IL-10–/– animals (p > 0.05). Furthermore, skin allograft survival after combined therapy was shorter in IL-10–/– versus wild-type recipients (MST 20 and 41 days, respectively, p < 0.001). IL-4-mediated signaling through Stat6 is dispensable for prolonged allograft survival induced by T-cell depletion plus DSG. In contrast, IL-10 appears to be important for prolonged allograft survival induced by combined therapy in this model.https://doi.org/10.3727/096368908786092748 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Clement Asiedu Patricio Andrades Peter D. Ray James F. George Judith M. Thomas |
spellingShingle |
Clement Asiedu Patricio Andrades Peter D. Ray James F. George Judith M. Thomas IL-10 and IL-4 in Skin Allograft Survival Induced by T-Cell Depletion plus Deoxyspergualin Cell Transplantation |
author_facet |
Clement Asiedu Patricio Andrades Peter D. Ray James F. George Judith M. Thomas |
author_sort |
Clement Asiedu |
title |
IL-10 and IL-4 in Skin Allograft Survival Induced by T-Cell Depletion plus Deoxyspergualin |
title_short |
IL-10 and IL-4 in Skin Allograft Survival Induced by T-Cell Depletion plus Deoxyspergualin |
title_full |
IL-10 and IL-4 in Skin Allograft Survival Induced by T-Cell Depletion plus Deoxyspergualin |
title_fullStr |
IL-10 and IL-4 in Skin Allograft Survival Induced by T-Cell Depletion plus Deoxyspergualin |
title_full_unstemmed |
IL-10 and IL-4 in Skin Allograft Survival Induced by T-Cell Depletion plus Deoxyspergualin |
title_sort |
il-10 and il-4 in skin allograft survival induced by t-cell depletion plus deoxyspergualin |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2008-06-01 |
description |
The mechanisms mediating T-cell depletion plus 15-deoxyspergualin (DSG)-induced prolonged allograft survival or tolerance are uncertain. The purpose of this study is to evaluate the role of IL-4 and IL-10 in prolonged allograft survival induced by T-cell depletion plus DSG. MHC mismatched skin allograft transplantation was performed, using wild-type and three separate knockout (i.e., IL-4–/–, Stat6–/-, or IL-10–/–) mice as recipients. Induction therapy consisted of T-cell depletion and or brief course of DSG. The data demonstrate that monotherapy with T-cell-depleting mAbs or DSG prolonged skin allograft survival, compared to controls, in wild-type Balb/c recipients [median survival time (MST) = 25 and 21 vs. 10 days, p < 0.007]. T-cell depletion plus DSG further augmented skin allograft survival in wild-type animals relative to monotherapy (MST = 35 days vs. 25 and 21 days, p < 0.006 vs. mAbs or DSG only), and was equally effective in IL-4–/– and Stat6–/– recipients. In contrast, combined therapy was no better than monotherapy in IL-10–/– animals (p > 0.05). Furthermore, skin allograft survival after combined therapy was shorter in IL-10–/– versus wild-type recipients (MST 20 and 41 days, respectively, p < 0.001). IL-4-mediated signaling through Stat6 is dispensable for prolonged allograft survival induced by T-cell depletion plus DSG. In contrast, IL-10 appears to be important for prolonged allograft survival induced by combined therapy in this model. |
url |
https://doi.org/10.3727/096368908786092748 |
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