Vascularized Composite Allograft Rejection Is Delayed by Intrajejunal Treatment with Donor Splenocytes without Concomitant Immunosuppressants

Background. Mucosal or oral tolerance, an established method for inducing low-risk antigen-specific hyporesponsiveness, has not been investigated in vascularized composite allograft (VCA) research. We studied its effects on recipient immune responses and VCA rejection. Methods. Lewis rats (; TREATED...

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Main Authors: Christopher Glenn Wallace, Chia-Hung Yen, Hsiang-Chen Yang, Chun-Yen Lin, Ren-Chin Wu, Wei-Chao Huang, Jeng-Yee Lin, Fu-Chan Wei
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2012/704063
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author Christopher Glenn Wallace
Chia-Hung Yen
Hsiang-Chen Yang
Chun-Yen Lin
Ren-Chin Wu
Wei-Chao Huang
Jeng-Yee Lin
Fu-Chan Wei
author_facet Christopher Glenn Wallace
Chia-Hung Yen
Hsiang-Chen Yang
Chun-Yen Lin
Ren-Chin Wu
Wei-Chao Huang
Jeng-Yee Lin
Fu-Chan Wei
author_sort Christopher Glenn Wallace
collection DOAJ
description Background. Mucosal or oral tolerance, an established method for inducing low-risk antigen-specific hyporesponsiveness, has not been investigated in vascularized composite allograft (VCA) research. We studied its effects on recipient immune responses and VCA rejection. Methods. Lewis rats (; TREATED) received seven daily intrajejunal treatments of splenocytes from semiallogeneic Lewis-Brown-Norway rats (LBN) or vehicle (; SHAM). Recipients’ immune responses were assessed by mixed lymphocyte reaction (MLR) against donor antigen and controls. Other Lewis (; TREATED/VCA) received LBN hindlimb VCA and daily intrajejunal treatments of LBN splenocytes, or LBN VCA without treatment (; SHAM/VCA), until VCAs rejected. Recipients’ immune responses were characterised and VCAs biopsied for histopathology. Immunosuppressants were not used. Results. LBN-specific hyporesponsiveness was induced only in treated Lewis recipients. Treatment significantly reduced MLR alloreactivity, significantly reduced VCA rejection on histopathology, and significantly delayed clinical VCA rejection (; TREATED/VCA mean 9.6 versus 6.0 days for SHAM/VCA). Treatment significantly increased immunosuppressive IL-10/IL-4/TGF-β production and significantly decreased proinflammatory IFN-γ/TNF-α. Conclusion. Jejunal exposure to antigen conferred donor specific hyporesponsiveness that delayed VCA rejection. This method may offer a low-risk adjunctive treatment option to help protect VCAs from rejection.
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spelling doaj-art-b56a3a86366440ca9d989fda1b0fc4b92025-02-03T01:12:04ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/704063704063Vascularized Composite Allograft Rejection Is Delayed by Intrajejunal Treatment with Donor Splenocytes without Concomitant ImmunosuppressantsChristopher Glenn Wallace0Chia-Hung Yen1Hsiang-Chen Yang2Chun-Yen Lin3Ren-Chin Wu4Wei-Chao Huang5Jeng-Yee Lin6Fu-Chan Wei7Department of Plastic Surgery, Chang Gung Memorial Hospital, Chang Gung University and Medical College, 199 Tun Hwa North Road, Taipei 105, TaiwanDepartment of Biological Science and Technology, National Pingtung University of Science and Technology 1 Hseuh-Fu Road, Neipu 91201, Pingtung, TaiwanDepartment of Plastic Surgery, Chang Gung Memorial Hospital, Chang Gung University and Medical College, 199 Tun Hwa North Road, Taipei 105, TaiwanDepartment of Hepatogastroenterology, Chang Gung Memorial Hospital, Chang Gung University and Medical College, 199 Tun Hwa North Road, Taipei 105, TaiwanDepartment of Pathology, Chang Gung Memorial Hospital, Chang Gung University and Medical College, 199 Tun Hwa North Road, Taipei 105, TaiwanDepartment of Plastic Surgery, Chang Gung Memorial Hospital, Chia-Yi, TaiwanDepartment of Plastic Surgery, Chang Gung Memorial Hospital, Chang Gung University and Medical College, 199 Tun Hwa North Road, Taipei 105, TaiwanDepartment of Plastic Surgery, Chang Gung Memorial Hospital, Chang Gung University and Medical College, 199 Tun Hwa North Road, Taipei 105, TaiwanBackground. Mucosal or oral tolerance, an established method for inducing low-risk antigen-specific hyporesponsiveness, has not been investigated in vascularized composite allograft (VCA) research. We studied its effects on recipient immune responses and VCA rejection. Methods. Lewis rats (; TREATED) received seven daily intrajejunal treatments of splenocytes from semiallogeneic Lewis-Brown-Norway rats (LBN) or vehicle (; SHAM). Recipients’ immune responses were assessed by mixed lymphocyte reaction (MLR) against donor antigen and controls. Other Lewis (; TREATED/VCA) received LBN hindlimb VCA and daily intrajejunal treatments of LBN splenocytes, or LBN VCA without treatment (; SHAM/VCA), until VCAs rejected. Recipients’ immune responses were characterised and VCAs biopsied for histopathology. Immunosuppressants were not used. Results. LBN-specific hyporesponsiveness was induced only in treated Lewis recipients. Treatment significantly reduced MLR alloreactivity, significantly reduced VCA rejection on histopathology, and significantly delayed clinical VCA rejection (; TREATED/VCA mean 9.6 versus 6.0 days for SHAM/VCA). Treatment significantly increased immunosuppressive IL-10/IL-4/TGF-β production and significantly decreased proinflammatory IFN-γ/TNF-α. Conclusion. Jejunal exposure to antigen conferred donor specific hyporesponsiveness that delayed VCA rejection. This method may offer a low-risk adjunctive treatment option to help protect VCAs from rejection.http://dx.doi.org/10.1155/2012/704063
spellingShingle Christopher Glenn Wallace
Chia-Hung Yen
Hsiang-Chen Yang
Chun-Yen Lin
Ren-Chin Wu
Wei-Chao Huang
Jeng-Yee Lin
Fu-Chan Wei
Vascularized Composite Allograft Rejection Is Delayed by Intrajejunal Treatment with Donor Splenocytes without Concomitant Immunosuppressants
Clinical and Developmental Immunology
title Vascularized Composite Allograft Rejection Is Delayed by Intrajejunal Treatment with Donor Splenocytes without Concomitant Immunosuppressants
title_full Vascularized Composite Allograft Rejection Is Delayed by Intrajejunal Treatment with Donor Splenocytes without Concomitant Immunosuppressants
title_fullStr Vascularized Composite Allograft Rejection Is Delayed by Intrajejunal Treatment with Donor Splenocytes without Concomitant Immunosuppressants
title_full_unstemmed Vascularized Composite Allograft Rejection Is Delayed by Intrajejunal Treatment with Donor Splenocytes without Concomitant Immunosuppressants
title_short Vascularized Composite Allograft Rejection Is Delayed by Intrajejunal Treatment with Donor Splenocytes without Concomitant Immunosuppressants
title_sort vascularized composite allograft rejection is delayed by intrajejunal treatment with donor splenocytes without concomitant immunosuppressants
url http://dx.doi.org/10.1155/2012/704063
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