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...
Main Authors: | , , , , |
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Format: | Article |
Language: | English |
Published: |
SAGE Publishing
2008-06-01
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Series: | Cell Transplantation |
Online Access: | https://doi.org/10.3727/096368908786092748 |
Summary: | 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. |
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ISSN: | 0963-6897 1555-3892 |