We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Adenoviral transfer of a single donor-specific MHC class I gene to recipient bone marrow cells can induce specific immunological unresponsiveness in vivo.
- Authors
Fry, J.W.; Morris, P.J.; Wood, K.J.
- Abstract
We investigated the delivery of a donor-specific MHC class I gene, H-2K[sup b], using a newly constructed replication-defective recombinant adenovirus (AdSV40K[sup b]) to recipient tissue before transplantation as a means of inducing donor-specific immunological unresponsiveness. AdSV40K[sup b] was able to transduce both a fibroblast cell line and freshly isolated bone marrow cells (BMCs) resulting in cell surface expression of H2-K[sup b] protein. Intravenous infusion of AdSV4OK[sup b]-transduced syngeneic CBA/Ca (H-2[sup k]) BMCs into CBA recipient mice treated with an anti-CD4 monoclonal antibody 27 days before transplantation of a fully MHC-mismatched, C57BL/10 (H-2K[sup b+]), 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-2K[sup b]- specific hyporesponsiveness following pretreatment with AdSV4OK[sup b]-transduced CBA BMCs, persistence of H-2K[sup b] mRNA in central or peripheral tissues could not be demonstrated by RT-PCR. This result was in contrast to the observed persistence of K[sup b] mRNA both in the periphery and thymus following the infusion of transgenic CBK (H-2[sup k] + K[sup b]) 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[sup +] 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.
- Subjects
GENETIC transformation; ADENOVIRUSES; MAJOR histocompatibility complex; BONE marrow cells; IMMUNE response
- Publication
Gene Therapy, 2002, Vol 9, Issue 3, p220
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301648