Induction therapy with monoclonal antibodies specific for CD80 and CD86 delays the onset of acute renal allograft rejection in non-human primates.

Published

Journal Article

CD80 and CD86 (also known as B7-1 and B7-2, respectively) are both ligands for the T cell costimulatory receptors CD28 and CD152. Both CD80 and CD86 mediate T cell costimulation, and as such, have been studied for their role in promoting allograft rejection. In this study we demonstrate that administering monoclonal antibodies specific for these B7 ligands can delay the onset of acute renal allograft rejection in rhesus monkeys. The most durable effect results from simultaneous administration of both anti-B7 antibodies. The mechanism of action does not involve global depletion of T or B cells. Despite in vitro and in vivo evidence demonstrating the effectiveness of the anti-B7 antibodies in suppressing T cell responsiveness to alloantigen, their use does not result in durable tolerance. Prolonged therapy with murine anti-B7 antibodies is limited by the development of neutralizing antibodies, but that problem was avoided when humanized anti-B7 reagents are used. Most animals develop rejection and an alloantibody response although still on antibody therapy and before the development of a neutralizing antibody response. Anti-B7 antibody therapy may have use as an adjunctive agent for clinical allotransplantation, but using the dosing regimens we used, is not a tolerizing therapy in this non-human primate model.

Full Text

Duke Authors

Cited Authors

  • Kirk, AD; Tadaki, DK; Celniker, A; Batty, DS; Berning, JD; Colonna, JO; Cruzata, F; Elster, EA; Gray, GS; Kampen, RL; Patterson, NB; Szklut, P; Swanson, J; Xu, H; Harlan, DM

Published Date

  • August 15, 2001

Published In

Volume / Issue

  • 72 / 3

Start / End Page

  • 377 - 384

PubMed ID

  • 11502964

Pubmed Central ID

  • 11502964

International Standard Serial Number (ISSN)

  • 0041-1337

Digital Object Identifier (DOI)

  • 10.1097/00007890-200108150-00005

Language

  • eng

Conference Location

  • United States