Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

We investigated the delivery of a donor-specific MHC class I gene, H-2Kb, using a newly constructed replication-defective recombinant adenovirus (AdSV40Kb) to recipient tissue before transplantation as a means of inducing donor-specific immunological unresponsiveness. AdSV40Kbwas able to transduce both a fibroblast cell line and freshly isolated bone marrow cells (BMCs) resulting in cell surface expression of H2-Kbprotein. Intravenous infusion of AdSV40Kb-transduced syngeneic CBA/Ca (H-2k) BMCs into CBA recipient mice treated with an anti-CD4 monoclonal antibody 27 days before transplantation of a fully MHC-mismatched, C57BL/10 (H-2Kb+), cardiac allograft resulted in significant long-term graft survival when compared with mice receiving the same dose of syngeneic BMCs transduced with a control adenovirus, AdRSVβgal. Despite the induction of H-2Kb-specific hyporesponsiveness following pretreatment with AdSV40Kb-transduced CBA BMCs, persistence of H-2KbmRNA in central or peripheral tissues could not be demonstrated by RT-PCR. This result was in contrast to the observed persistence of KbmRNA both in the periphery and thymus following the infusion of transgenic CBK (H-2k+ Kb) BMCs. We conclude that ex vivo adenoviral gene transfer of a single donor MHC class I gene to recipient BMCs in combination with transient depletion of CD4+cells is sufficient to induce long-term graft survival of a fully allogeneic cardiac graft. In addition, detectable microchimerism is not a prerequisite for graft survival.

Original publication

DOI

10.1038/sj.gt.3301648

Type

Journal article

Journal

Gene Therapy

Publication Date

01/01/2002

Volume

9

Pages

220 - 226