CD154 blockade for induction of mixed chimerism and prolonged renal allograft survival in nonhuman primates

Tatsuo Kawai, Hiroshi Sogawa, Svetlan Boskovic, Gregory Abrahamian, Rex Neal Smith, Siew Lin Wee, David Andrews, Ognjenka Nadazdin, Ichiro Koyama, Megan Sykes, Henry J. Winn, Robert B. Colvin, David H. Sachs, A. Benedict Cosimi

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

Costimulatory blockade with anti-CD154 monoclonal antibody (aCD154) prolongs allograft survival in non-human 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.

Original languageEnglish (US)
Pages (from-to)1391-1398
Number of pages8
JournalAmerican Journal of Transplantation
Volume4
Issue number9
DOIs
StatePublished - Sep 1 2004
Externally publishedYes

Keywords

  • CD154 blockade
  • Kidney transplantation
  • Mixed chimerism
  • Tolerance

ASJC Scopus subject areas

  • Immunology

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    Kawai, T., Sogawa, H., Boskovic, S., Abrahamian, G., Smith, R. N., Wee, S. L., Andrews, D., Nadazdin, O., Koyama, I., Sykes, M., Winn, H. J., Colvin, R. B., Sachs, D. H., & Cosimi, A. B. (2004). CD154 blockade for induction of mixed chimerism and prolonged renal allograft survival in nonhuman primates. American Journal of Transplantation, 4(9), 1391-1398. https://doi.org/10.1111/j.1600-6143.2004.00523.x