期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 4, 期 9, 页码 1391-1398出版社
BLACKWELL MUNKSGAARD
DOI: 10.1111/j.1600-6143.2004.00523.x
关键词
CD154 blockade; kidney transplantation; mixed chimerism; tolerance
资金
- NHLBI NIH HHS [P0I-HL18646] Funding Source: Medline
- NIAID NIH HHS [R01 AI037692, R01 AI037692-09, R01 AI037692-10, R21 AI037692, R21 AI037692-06, 5R01 AI50987-03] Funding Source: Medline
- PHS HHS [R0I A137692] Funding Source: Medline
Costimulatory blockade with anti-CD154 monoclonal antibody (aCD154) prolongs allograft survival in nonhuman primates, but has not reliably induced tolerance when used alone. In the current studies, we evaluated the effect of adding CD154 blockade to a chimerism inducing nonmyeloablative regimen in primates. We observed a significant improvement of donor bone marrow (DBM) engraftment, which has been associated with a lower incidence of acute rejection and long-term survival of renal allografts without the need for previously required splenectomy. Among the long-term survivors, four never showed evidence of rejection, with the longest survival exceeding 1700 days following discontinuation of immunosuppression. Nevertheless, late chronic rejection was observed in three of eight recipients, indicating the necessity of further modifications of the regimen. Control recipients receiving no DBM or donor splenocytes in place of DBM rejected their allografts. Thus, DBM engraftment with, at least, transient mixed chimerism appears essential for induction of allograft tolerance using this conditioning regimen. Modification of the original mixed chimerism approach, by the addition of costimulatory blockade, has been shown to enhance mixed chimerism and induce renal allograft tolerance with less morbidity in nonhuman primates.
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