Treatment with humanized monoclonal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates.

Published

Journal Article

CD154 is the ligand for the receptor CD40. This ligand-receptor pair mediates endothelial and antigen-presenting cell activation, and facilitates the interaction of these cells with T cells and platelets. We demonstrate here that administration of a CD154-specific monoclonal antibody (hu5C8) allows for renal allotransplantation in outbred, MHC-mismatched rhesus monkeys without acute rejection. The effect persisted for more than 10 months after therapy termination, and no additional drug was required to achieve extended graft survival. Indeed, the use of tacrolimus or chronic steroids seemed to antagonize the anti-rejection effect. Monkeys treated with antibody against CD154 remained healthy during and after therapy. The mechanism of action does not require global depletion of T or B cells. Long-term survivors lost their mixed lymphocyte reactivity in a donor-specific manner, but still formed donor-specific antibody and generated T cells that infiltrated the grafted organ without any obvious effect on graft function. Thus, therapy with antibody against CD154 is a promising agent for clinical use in human allotransplantation.

Full Text

Duke Authors

Cited Authors

  • Kirk, AD; Burkly, LC; Batty, DS; Baumgartner, RE; Berning, JD; Buchanan, K; Fechner, JH; Germond, RL; Kampen, RL; Patterson, NB; Swanson, SJ; Tadaki, DK; TenHoor, CN; White, L; Knechtle, SJ; Harlan, DM

Published Date

  • June 1999

Published In

Volume / Issue

  • 5 / 6

Start / End Page

  • 686 - 693

PubMed ID

  • 10371508

Pubmed Central ID

  • 10371508

International Standard Serial Number (ISSN)

  • 1078-8956

Digital Object Identifier (DOI)

  • 10.1038/9536

Language

  • eng

Conference Location

  • United States