Tolerance to MHC class II disparate allografts through genetic modification of bone marrow

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Tolerance to MHC class II disparate allografts through genetic modification of bone marrow

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Title: Tolerance to MHC class II disparate allografts through genetic modification of bone marrow
Author: Jindra, Peter T.; Tripathi, Sudipta; Tian, Chaorui; Iacomini, John; Bagley, Jessamyn

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Citation: 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.
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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.
Published Version: doi:10.1038/gt.2012.57
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651743/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879126
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