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T-cell-mediated immunological barriers to xenotransplantation.

Authors
  • Scalea, Joseph
  • Hanecamp, Isabel
  • Robson, Simon C
  • Yamada, Kazuhiko
Type
Published Article
Journal
Xenotransplantation
Publication Date
Jan 01, 2012
Volume
19
Issue
1
Pages
23–30
Identifiers
DOI: 10.1111/j.1399-3089.2011.00687.x
PMID: 22360750
Source
Medline
License
Unknown

Abstract

Xenotransplantion remains the most viable option for significant expansion of the donor organ pool in clinical transplantation. With the advent of nuclear transfer technologies, the production of transgenic swine has become a possibility. These animals have allowed transplant investigators to overcome humoral mechanisms of hyperacute xenograft rejection in experimental pig-to-non-human primate models. However, other immunologic barriers preclude long-term acceptance of xenografts. This review article focuses on a major feature of xenogeneic rejection: xenogeneic T cell responses. Evidence obtained from both small and large animal models, particularly those using either islet cells or kidneys, have demonstrated that T cell responses play a major role in xenogeneic rejection, and that immunosuppression alone is likely incapable of completely suppressing these responses. Additionally, both the direct and indirect pathway of antigen presentation appear to be involved in these anti donor processes. Enhanced understanding of (i) CD47 and its role in transduced xeno-bone marrow (ii) CD39 and its role in coagulation dysregulation and (iii) thymic transplantation have provided us with encouraging results. Presently, experiments evaluating the possibility of xenogeneic tolerance are underway.

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