CD154 Blockade and Donor-Specific Transfusions in DLA-Identical Marrow Transplantation in Dogs Conditioned with 1 Gy Total Body Irradiation
Identifieur interne : 000E88 ( Main/Exploration ); précédent : 000E87; suivant : 000E89CD154 Blockade and Donor-Specific Transfusions in DLA-Identical Marrow Transplantation in Dogs Conditioned with 1 Gy Total Body Irradiation
Auteurs : Christoph Jochum ; Mechthild Beste ; Eustacia Zellmer ; Scott S. Graves ; Rainer StorbSource :
- Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [ 1083-8791 ] ; 2007.
Abstract
Stable mixed donor/host chimerism has been reliably established in dogs given a sublethal dose of 2 Gy total body irradiation (TBI) before and immunosuppression with mycophenolate mofetil (MMF) or rapamycin combined with cyclosporine (CSP) after marrow transplantation from DLA-identical littermates (HCT). When TBI was reduced to 1 Gy, only transient engraftment was observed. Here we asked whether stable engraftment after 1 Gy TBI could be accomplished by reducing host vs. donor immune responsiveness through preceding CD154 blockade and infusion of donor peripheral blood mononuclear cells (PBMC). The anti-human CD154 antibody, 5c8, cross-reacted with canine lymphocytes and blocked allo-immune responses in vitro. Based on pharmacokinetic studies, six dogs received a single i.v. injection of 5 mg/kg anti-CD154 antibody (day -5) followed one day later by donor PBMC. On day 0, dogs were given 1 Gy TBI and DLA-identical marrow grafts. Postgrafting immunosuppression consisted of MMF and CSP. All six dogs showed initial engraftment, which was sustained in three of the six for >26 weeks, while three dogs rejected their grafts after 9, 22, and 24 weeks, respectively, and survived with autologous recovery. Graft survival was significantly improved over that among 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 (
Url:
DOI: 10.1016/j.bbmt.2006.10.031
PubMed: 17241922
PubMed Central: 1831459
Affiliations:
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Graves</name><affiliation><nlm:aff id="A1">Transplantation Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center; 1100 Fairview Avenue N, D1-100, PO Box 19024, Seattle, WA, USA, 98109-1024.</nlm:aff><wicri:noCountry code="subfield">98109-1024.</wicri:noCountry></affiliation></author><author><name sortKey="Storb, Rainer" sort="Storb, Rainer" uniqKey="Storb R" first="Rainer" last="Storb">Rainer Storb</name><affiliation><nlm:aff id="A1">Transplantation Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center; 1100 Fairview Avenue N, D1-100, PO Box 19024, Seattle, WA, USA, 98109-1024.</nlm:aff><wicri:noCountry code="subfield">98109-1024.</wicri:noCountry></affiliation><affiliation><nlm:aff id="A2">Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA, 98195.</nlm:aff><wicri:noCountry code="subfield">98195.</wicri:noCountry></affiliation></author></analytic><series><title level="j">Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation</title><idno type="ISSN">1083-8791</idno><idno type="eISSN">1523-6536</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Stable mixed donor/host chimerism has been reliably established in dogs given a sublethal dose of 2 Gy total body irradiation (TBI) before and immunosuppression with mycophenolate mofetil (MMF) or rapamycin combined with cyclosporine (CSP) after marrow transplantation from DLA-identical littermates (HCT). When TBI was reduced to 1 Gy, only transient engraftment was observed. Here we asked whether stable engraftment after 1 Gy TBI could be accomplished by reducing host vs. donor immune responsiveness through preceding CD154 blockade and infusion of donor peripheral blood mononuclear cells (PBMC). The anti-human CD154 antibody, 5c8, cross-reacted with canine lymphocytes and blocked allo-immune responses in vitro. Based on pharmacokinetic studies, six dogs received a single i.v. injection of 5 mg/kg anti-CD154 antibody (day -5) followed one day later by donor PBMC. On day 0, dogs were given 1 Gy TBI and DLA-identical marrow grafts. Postgrafting immunosuppression consisted of MMF and CSP. All six dogs showed initial engraftment, which was sustained in three of the six for >26 weeks, while three dogs rejected their grafts after 9, 22, and 24 weeks, respectively, and survived with autologous recovery. Graft survival was significantly improved over that among 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 (<italic>P</italic> = 0.03). Preceding donor PBMC infusion and CD154 blockade improved survival of DLA-identical marrow grafts after 1 Gy TBI.</p></div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Beste, Mechthild" sort="Beste, Mechthild" uniqKey="Beste M" first="Mechthild" last="Beste">Mechthild Beste</name><name sortKey="Graves, Scott S" sort="Graves, Scott S" uniqKey="Graves S" first="Scott S." last="Graves">Scott S. Graves</name><name sortKey="Jochum, Christoph" sort="Jochum, Christoph" uniqKey="Jochum C" first="Christoph" last="Jochum">Christoph Jochum</name><name sortKey="Storb, Rainer" sort="Storb, Rainer" uniqKey="Storb R" first="Rainer" last="Storb">Rainer Storb</name><name sortKey="Zellmer, Eustacia" sort="Zellmer, Eustacia" uniqKey="Zellmer E" first="Eustacia" last="Zellmer">Eustacia Zellmer</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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