PMID- 14511242
OWN - NLM
STAT- MEDLINE
DCOM- 20031024
LR  - 20190513
IS  - 0019-2805 (Print)
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Linking)
VI  - 110
IP  - 2
DP  - 2003 Oct
TI  - Simultaneous administration of a low-dose mixture of donor bone marrow cells and 
      splenocytes plus adenovirus containing the CTLA4Ig gene result in stable mixed 
      chimerism and long-term survival of cardiac allograft in rats.
PG  - 275-86
AB  - T-cell costimulatory blockade combined with donor bone marrow transfusion may 
      induce mixed chimerism, rendering robust tolerance in transplanted organs and 
      cells. However, most protocols entail high doses of donor bone marrow cells 
      (BMCs) or repeated administration of costly agents that block costimulatory 
      pathways, thus delaying clinical development. To circumvent these shortcomings, 
      we developed a strategy in which the dosage of donor BMCs was reduced but 
      compensated by donor splenocytes (SPLCs). Furthermore, repeated administration of 
      costly agents was replaced with a single injection of adenovirus expressing a 
      gene of interest. In rat cardiac transplantation models, cardiac allografts from 
      DA (RT-1a) rats were transplanted heterotopically into the abdomen of LEW (RT-11) 
      recipient rats. Immediately after cardiac transplantation, an adenovirus vector 
      (AdCTLA4Ig; 5 x 10(9) plaque-forming units) containing the gene for CTLA4Ig was 
      administered to recipients (n = 6) simultaneously with a low dose of donor BMCs 
      (1 x 10(8)/rat) and SPLCs (5 x 10(7)/rat) via the portal vein. The treated LEW 
      recipient rats developed long-lasting mixed chimerism (>10% at >100 days) and 
      exhibited long-term cardiac allografts (mean survival time of > 200 days) 
      compared with control recipients. Moreover, recipients displaying long-lasting 
      mixed chimerism accepted subsequent donor skin allografts while promptly 
      rejecting third-party skin allografts. These results suggest that blockade of the 
      CD28-B7 pathway, using adenovirus-mediated CTLA4Ig gene transfer, in concert with 
      a low dosage of donor BMCs and SPLCs, may represent a feasible strategy to induce 
      stable mixed chimerism and permit long-term survival of cardiac allografts.
FAU - Jin, Yongzhu
AU  - Jin Y
AD  - Department of Immunology, Peking University Health Science Center, Beijing, 
      China.
FAU - Zhang, Qingyin
AU  - Zhang Q
FAU - Hao, Jie
AU  - Hao J
FAU - Gao, Xiang
AU  - Gao X
FAU - Guo, Yinglu
AU  - Guo Y
FAU - Xie, Shusheng
AU  - Xie S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Immunoconjugates)
RN  - 7D0YB67S97 (Abatacept)
SB  - IM
MH  - Abatacept
MH  - Adenoviridae/genetics
MH  - Adoptive Transfer
MH  - Animals
MH  - Bone Marrow Transplantation/*immunology
MH  - Genetic Therapy/methods
MH  - Genetic Vectors
MH  - Graft Survival/immunology
MH  - Graft vs Host Disease/prevention & control
MH  - Heart Transplantation/*immunology
MH  - Immunoconjugates/blood/*genetics
MH  - Lymphocyte Culture Test, Mixed
MH  - Male
MH  - Myocardium/pathology
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Rats, Inbred Strains
MH  - Rats, Inbred WF
MH  - Skin Transplantation/immunology
MH  - Spleen/*transplantation
MH  - Transplantation Chimera/immunology
MH  - Transplantation Tolerance/*immunology
PMC - PMC1783046
EDAT- 2003/09/27 05:00
MHDA- 2003/10/25 05:00
PMCR- 2004/10/01
CRDT- 2003/09/27 05:00
PHST- 2003/09/27 05:00 [pubmed]
PHST- 2003/10/25 05:00 [medline]
PHST- 2003/09/27 05:00 [entrez]
PHST- 2004/10/01 00:00 [pmc-release]
AID - 1729 [pii]
AID - 10.1046/j.1365-2567.2003.01729.x [doi]
PST - ppublish
SO  - Immunology. 2003 Oct;110(2):275-86. doi: 10.1046/j.1365-2567.2003.01729.x.