Tolerance to MHC class II disparate allografts through genetic modification of bone marrow
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Author
Jindra, Peter T.
Tripathi, Sudipta
Tian, Chaorui
Iacomini, John
Bagley, Jessamyn
Published Version
https://doi.org/10.1038/gt.2012.57Metadata
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Jindra, Peter T., Sudipta Tripathi, Chaorui Tian, John Iacomini, and Jessamyn Bagley. 2012. “Tolerance to MHC class II disparate allografts through genetic modification of bone marrow.” Gene therapy 20 (5): 478-486. doi:10.1038/gt.2012.57. http://dx.doi.org/10.1038/gt.2012.57.Abstract
Induction of molecular chimerism through genetic modification of bone marrow is a powerful tool for the induction of tolerance. Here we demonstrate for the first time that expression of an allogeneic MHC class II gene in autologous bone marrow cells, resulting in a state of molecular chimerism, induces tolerance to MHC class II mismatched skin grafts, a stringent test of transplant tolerance. Reconstitution of recipients with syngeneic bone marrow transduced with retrovirus encoding H-2I-Ab (I-Ab) resulted the long-term expression of the retroviral gene product on the surface of MHC class II-expressing bone marrow derived cell types. Mechanistically, tolerance was maintained by the presence of regulatory T cells, which prevented proliferation and cytokine production by alloreactive host T cells. Thus, the introduction of MHC class II genes into bone marrow derived cells through genetic engineering results in tolerance. These results have the potential to extend the clinical applicability of molecular chimerism for tolerance induction.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651743/pdf/Terms of Use
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