CD154 blockade and donor-specific transfusions in DLA-identical marrow transplantation in dogs conditioned with 1-Gy total body irradiation.
Biol Blood Marrow Transplant
; 13(2): 164-71, 2007 Feb.
Article
em En
| MEDLINE
| ID: mdl-17241922
ABSTRACT
Stable mixed donor/host chimerism has been reliably established in dogs given a sublethal dose (2 Gy) of total body irradiation (TBI) before and immunosuppression with mycophenolate mofetil (MMF) or rapamycin combined with cyclosporine (CSP) after marrow transplantation from dog leukocyte antigen (DLA)-identical littermates (hematopoietic cell transplantation [HCT]). When TBI was reduced to 1 Gy, only transient engraftment was observed. Here we investigated whether stable engraftment after 1-Gy TBI could be accomplished by reducing host-versus-donor immune responsiveness through preceding CD154 blockade and infusion of donor peripheral blood mononuclear cells (PBMCs). We found that the anti-human CD154 antibody, 5c8, cross-reacted with canine lymphocytes and blocked alloimmune responses in vitro. Based on pharmacokinetic studies, 6 dogs received a single intravenous injection of 5 mg/kg anti-CD154 antibody (on day -5), followed 1 day later by donor PBMCs. On day 0, the dogs were given 1 Gy of TBI and underwent DLA-identical marrow grafts. Postgraft immunosuppression consisted of MMF and CSP. All 6 dogs demonstrated initial engraftment; 3 dogs sustained the engraftment for >26 weeks, whereas 3 dogs rejected their grafts, after 9, 22, and 24 weeks, and survived with autologous recovery. Graft survival was significantly improved over that in 11 historical controls conditioned with 1-Gy TBI and given either MMF or rapamycin with CSP after HCT, all of which rejected their grafts between 3 and 12 weeks (P = .03). Preceding donor PBMC infusion and CD154 blockade improved survival of DLA-identical marrow grafts after 1-Gy TBI.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Irradiação Corporal Total
/
Transplante de Medula Óssea
/
Transfusão de Leucócitos
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Condicionamento Pré-Transplante
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Ligante de CD40
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Sobrevivência de Enxerto
/
Soro Antilinfocitário
Limite:
Animals
Idioma:
En
Revista:
Biol Blood Marrow Transplant
Assunto da revista:
HEMATOLOGIA
/
TRANSPLANTE
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos