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Clinical and Developmental Immunology
Volume 2012 (2012), Article ID 704063, 11 pages
http://dx.doi.org/10.1155/2012/704063
Research Article

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

1Department of Plastic Surgery, Chang Gung Memorial Hospital, Chang Gung University and Medical College, 199 Tun Hwa North Road, Taipei 105, Taiwan
2Department of Biological Science and Technology, National Pingtung University of Science and Technology 1 Hseuh-Fu Road, Neipu 91201, Pingtung, Taiwan
3Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Chang Gung University and Medical College, 199 Tun Hwa North Road, Taipei 105, Taiwan
4Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University and Medical College, 199 Tun Hwa North Road, Taipei 105, Taiwan
5Department of Plastic Surgery, Chang Gung Memorial Hospital, Chia-Yi, Taiwan

Received 4 May 2012; Accepted 12 October 2012

Academic Editor: Gerald Brandacher

Copyright © 2012 Christopher Glenn Wallace et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.