PMID- 11859426
OWN - NLM
STAT- MEDLINE
DCOM- 20020408
LR  - 20171116
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 9
IP  - 3
DP  - 2002 Feb
TI  - Adenoviral transfer of a single donor-specific MHC class I gene to recipient bone 
      marrow cells can induce specific immunological unresponsiveness in vivo.
PG  - 220-6
AB  - We investigated the delivery of a donor-specific MHC class I gene, H-2K(b), using 
      a newly constructed replication-defective recombinant adenovirus (AdSV40K(b)) to 
      recipient tissue before transplantation as a means of inducing donor-specific 
      immunological unresponsiveness. AdSV40K(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(b) protein. Intravenous infusion of 
      AdSV40K(b)-transduced syngeneic CBA/Ca (H-2(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(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, AdRSVbetagal. 
      Despite the induction of H-2K(b)-specific hyporesponsiveness following 
      pretreatment with AdSV40K(b)-transduced CBA BMCs, persistence of H-2K(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(b) mRNA both in the periphery 
      and thymus following the infusion of transgenic CBK (H-2(k) + K(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(+) 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.
FAU - Fry, J W
AU  - Fry JW
AD  - Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, 
      Oxford, UK.
FAU - Morris, P J
AU  - Morris PJ
FAU - Wood, K J
AU  - Wood KJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (CD4 Antigens)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Antibodies, Monoclonal/administration & dosage
MH  - *Bone Marrow Cells/*immunology
MH  - Bone Marrow Transplantation
MH  - CD4 Antigens/immunology
MH  - *Genes, MHC Class I
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/administration & dosage
MH  - Graft vs Host Disease/*prevention & control
MH  - *Heart Transplantation
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred CBA
MH  - Transplantation Immunology
MH  - Transplantation, Homologous
EDAT- 2002/02/23 10:00
MHDA- 2002/04/09 10:01
CRDT- 2002/02/23 10:00
PHST- 2001/11/07 00:00 [received]
PHST- 2001/11/30 00:00 [accepted]
PHST- 2002/02/23 10:00 [pubmed]
PHST- 2002/04/09 10:01 [medline]
PHST- 2002/02/23 10:00 [entrez]
AID - 10.1038/sj.gt.3301648 [doi]
PST - ppublish
SO  - Gene Ther. 2002 Feb;9(3):220-6. doi: 10.1038/sj.gt.3301648.