Adenoviral transfer of a single donor-specific MHC class I gene to recipient bone marrow cells can induce specific immunological unresponsiveness in vivo

Fry, J; Morris, P; Wood, K

Journal article

Adenoviral transfer of a single donor-specific MHC class I gene to recipient bone marrow cells can induce specific immunological unresponsiveness in vivo

Abstract:: 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. AdSV40Kb was able to transduce both a fibroblast cell line and freshly isolated bone marrow cells (BMCs) resulting in cell surface expression of H2-Kb protein. 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-2Kb mRNA in central or peripheral tissues could not be demonstrated by RT-PCR. This result was in contrast to the observed persistence of Kb mRNA 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.

Publication status:: Published

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Cite

Cite this record

APA Style

Fry, J., Morris, P., & Wood, K. (2002). Adenoviral transfer of a single donor-specific MHC class I gene to recipient bone marrow cells can induce specific immunological unresponsiveness in vivo. GENE THERAPY, 9(3), 220–226.

MLA Style

Fry, J., et al. “Adenoviral Transfer of a Single Donor-Specific MHC Class I Gene to Recipient Bone Marrow Cells Can Induce Specific Immunological Unresponsiveness in Vivo.” GENE THERAPY, vol. 9, no. 3, 2002, pp. 220–26.

Chicago Style

Fry, J, P Morris, and K Wood. 2002. “Adenoviral Transfer of a Single Donor-Specific MHC Class I Gene to Recipient Bone Marrow Cells Can Induce Specific Immunological Unresponsiveness in Vivo.” GENE THERAPY 9 (3): 220–26.
Share
Print