Authors
Joel Trambley, Adam W Bingaman, Angello Lin, Eric T Elwood, Seung-Yeun Waitze, Jongwon Ha, Megan M Durham, Matthias Corbascio, Shannon R Cowan, Thomas C Pearson, Christian P Larsen
Publication date
1999/12/15
Journal
The Journal of clinical investigation
Volume
104
Issue
12
Pages
1715-1722
Publisher
American Society for Clinical Investigation
Description
Simultaneous blockade of the CD40 and CD28 costimulatory pathways is an effective treatment strategy to promote allograft acceptance but does not lead to indefinite allograft survival. The immune mechanisms responsible for costimulation-independent rejection are not defined. Here we have studied the rejection responses of murine C57BL/6 recipients, which we show to be relatively resistant to inhibition by combined CD40/CD28 blockade. We demonstrate that asialo GM1+ CD8+ cells play a critical role in this costimulation blockade–resistant rejection. These results provide new insights into the costimulatory requirements for T-cell subsets and demonstrate for the first time that combined blockade of the CD40 and CD28 pathways does not adequately inhibit CD8-mediated skin allograft rejection. Furthermore, we provide evidence that asialo GM1 is a potentially important therapeutic target for CD8-dependent …
Total citations
Scholar articles
J Trambley, AW Bingaman, A Lin, ET Elwood… - The Journal of clinical investigation, 1999