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Prolonged limb allograft survival with CD40 costimulation blockade, T‐cell depletion, and megadose donor bone‐marrow transfusion
Author(s) -
Tung Thomas H.,
Mackin Susan E.,
Mohanakumar T.
Publication year - 2005
Publication title -
microsurgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.031
H-Index - 63
eISSN - 1098-2752
pISSN - 0738-1085
DOI - 10.1002/micr.20170
Subject(s) - medicine , bone marrow , blockade , surgery , immunology , receptor
The purpose of this study was to determine the efficacy of a treatment regimen consisting of CD40 costimulation blockade, T‐cell depletion, and megadose donor bone marrow transfusion in the limb allograft model. C57Bl/6 mice underwent limb transplantation from Balb/c mice and received MR1 (anti‐CD40 ligand monoclonal antibody), and CD4 + and CD8 + T cell‐depleting antibodies with and without 120 × 10 6 donor bone‐marrow transfusion. Recipients treated only with antibodies showed rejection at 51.4 ± 17 (mean ± SEM) days, while those who also received donor bone marrow had allograft survival of 67 ± 16.4 days, with a range up to 91 days. Treated specimens with rejection had less lymphocytic infiltration than untreated controls. Recipients of donor bone marrow also demonstrated early mixed chimerism, which disappeared after 1 month. While allograft survival was prolonged, tolerance was not achieved, and the mechanism of rejection was more consistent with a chronic process. © 2005 Wiley‐Liss, Inc. Microsurgery 25:624–631, 2005.