Asialo GM1+ CD8+ T cells play a critical role in costimulation blockade–resistant allograft rejection
AUTOR(ES)
Trambley, Joel
FONTE
American Society for Clinical Investigation
RESUMO
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 immune responses.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=409885Documentos Relacionados
- The role of CD8+ T cells during allograft rejection
- CD4+CD25+ regulatory T cells suppress allograft rejection mediated by memory CD8+ T cells via a CD30-dependent mechanism
- Blockade of T cell costimulation reveals interrelated actions of CD4+ and CD8+ T cells in control of SIV replication
- Blockade of T-cell costimulation prevents development of experimental chronic renal allograft rejection.
- Late blockade of T cell costimulation interrupts progression of experimental chronic allograft rejection.
