Adenovirus-mediated CTLA4 immunoglobulin based conditioning for non-myeloablative allogeneic hematopoietic cell transplantation to induce tolerance to hind limb allografts in rats / 中华外科杂志
Chinese Journal of Surgery
;
(12): 937-940, 2009.
Article
in Chinese
| WPRIM
| ID: wpr-280563
ABSTRACT
<p><b>OBJECTIVE</b>To investigate a non-toxic AdCTLA4-Ig-based protocol for non-myeloablative allogeneic hematopoietic cell transplantation to induce donor-specific tolerance to hind limb allografts in rats.</p><p><b>METHODS</b>Fully mismatched, 4 to 8 week old Brown Norway (RT1(n)) and Lewis (RT1(1)) rats were used as cell/organ donors and recipients, respectively. Recipients were treated with AdCTLA4-Ig (5 x 10(9) PFU, day -30, 0, 30), standard immunosuppressive therapy (MP 10 mg x kg(-1) x d(-1), MMF 20 mg x kg(-1) x d(-1), RAPA 0.2 mg x kg(-1) x d(-1);day -33 - 100), soon after total body irradiation (3 Gy, day -30) and donor bone marrow (100 x 10(6), day -30) transplantation (BMT). Thirty days after BMT, chimeric animals received hind limb transplantations. And 100 days after hind limb transplantations, immunosuppressive therapy was changed for low-dosed CsA (8 mg x kg(-1) x d(-1), day 100-), until the allografts were rejected.</p><p><b>RESULTS</b>In Group C, hematopoietic chimerism was (38.8 +/- 10.6)% at day 0, and was stable (29.3 +/- 11.9)% at 330 days post-BMT. There was no graft versus host disease in both Group C and Group D. When the standard immunosuppressive therapy was stopped and changed for low-dosed CsA, chimeric recipients (Lewis, RT1(1)) permanently accepted (> 200 days) donor specific (Brown Norway, RT1(n)) hind limb allografts in Group C, yet rapidly rejected in Group A (8 +/- 2) d, Group B (18 +/- 3) d and in Group C (20 +/- 2) d. Lymphocytes of graft tolerant animals' demonstrated hyporesponsiveness in mixed lymphocyte cultures in a donor-specific manner in Group C. Tolerant graft histology showed no obliterative arteriopathy or chronic rejection.</p><p><b>CONCLUSION</b>The AdCTLA4-Ig based conditioning regimen with donor BMT produce stable mixed chimerism and induce donor-specific tolerance to hind limb allografts.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Rats, Inbred Lew
/
Rats, Inbred BN
/
Transplantation
/
Transplantation, Homologous
/
Random Allocation
/
Adenoviridae
/
Lymphocyte Culture Test, Mixed
/
Transplantation Chimera
/
Immunoconjugates
Type of study:
Practice guideline
Limits:
Animals
Language:
Chinese
Journal:
Chinese Journal of Surgery
Year:
2009
Type:
Article
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