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- Title
The degree of phylogenetic disparity of islet grafts dictates the reliance on indirect CD4 T-cell antigen recognition for rejection.
- Authors
Rayat, Gina R.; Johnson, Zachary A.; Beilke, Joshua N.; Korbutt, Gregory S.; Rajotte, Ray V.; Gill, Ronald G.
- Abstract
Cellular xenograft rejection involves a pronounced contribution of CD4 T-cells recognizing antigens in association with recipient MHC class II molecules. However, the requirement for such "indirect" antigen recognition for acute islet xenograft is not clear, especially as a function of the phylogenetic disparity between the donor and recipient species. In vitro studies show that C57BL/6 (B6) mouse T-cells respond directly to either allogeneic BALB/c or phylogenetically related xenogeneic WF rat stimulator cells while having undetectable responses to phylogenetically disparate porcine stimulator cells. Although all types of grafts rejected acutely in wild-type mice, this response demonstrated markedly differing dependence on host MHC class II antigen presentation, depending on the donor species. While BALB/c islet allografts were acutely rejected in B6 MHC class II-deficient (C2D) recipients, WF rat xenografts demonstrated marked prolongation in C2D hosts relative to wild-type recipients. Interestingly, neonatal porcine islet (NPI) xenografts uniformly survived long term (>100 days) in untreated C2D hosts despite transfer of wild-type CD4 T-cells, demonstrating that survival in C2D recipients was not secondary to a lack of CD4 T-cells seen in such mice. Taken together, these results show a marked hierarchy in the requirement for host MHC class II-restricted indirect pathway in the rejection of pancreatic islet grafts. Thus, while cellular rejection of porcine xenografts is generally quite vigorous, this pathway is relatively finite, displaying a major reliance on host MHC class II-dependent antigen presentation for acute rejection.
- Subjects
ISLANDS of Langerhans; CD4 antigen; GRAFT rejection; MAJOR histocompatibility complex
- Publication
Diabetes, 2003, Vol 52, Issue 6, p1433
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.52.6.1433