Survival of mouse pancreatic islet allografts in recipients treated with allogeneic small lymphocytes and antibody to CD40 ligand

David C. Parker, Dale L. Greiner, Nancy E. Phillips, Michael C. Appel, Alan W. Steele, Fiona H. Durie, Randolph J. Noelle, John P. Mordes, Aldo A. Rossini

Research output: Contribution to journalArticle

356 Scopus citations

Abstract

Combined treatment with allogeneic small lymphocytes or T-depleted small lymphocytes plus a blocking antibody to CD40 ligand (CD40L) permitted indefinite pancreatic islet allograft survival in 37 of 40 recipients that differed from islet donors at major and minor histocompatibility loci. The effect of the allogeneic small lymphocytes was donor antigen-specific. Neither treatment alone was as effective as combined treatment, although anti-CD40L by itself allowed indefinite islet allograft survival in 40% of recipients. Our interpretation is that small lymphocytes expressing donor antigens in the absence of appropriate costimulatory signals are tolerogenic for alloreactive host cells. Anti-CD40L antibody may prevent host T cells from inducing costimulatory signals in donor lymphocytes or islet grafts.

Original languageEnglish (US)
Pages (from-to)9560-9564
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number21
DOIs
StatePublished - Oct 10 1995

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Keywords

  • diabetes mellitus
  • islets of Langerhans
  • tolerance
  • transplantation

ASJC Scopus subject areas

  • General

Cite this

Parker, D. C., Greiner, D. L., Phillips, N. E., Appel, M. C., Steele, A. W., Durie, F. H., Noelle, R. J., Mordes, J. P., & Rossini, A. A. (1995). Survival of mouse pancreatic islet allografts in recipients treated with allogeneic small lymphocytes and antibody to CD40 ligand. Proceedings of the National Academy of Sciences of the United States of America, 92(21), 9560-9564. https://doi.org/10.1073/pnas.92.21.9560