Alloreactive (CD4-independent) CD8+ T cells jeopardize long-term survival of intrahepatic islet allografts Academic Article uri icon


MeSH Major

  • Graft Survival
  • Islets of Langerhans Transplantation


  • Despite success of early islet allograft engraftment and survival in humans, late islet allograft loss has emerged as an important clinical problem. CD8+ T cells that are independent of CD4+ T cell help can damage allograft tissues and are resistant to conventional immunosuppressive therapies. Previous work demonstrates that islet allografts do not primarily initiate rejection by the (CD4-independent) CD8-dependent pathway. This study was performed to determine if activation of alloreactive CD4-independent, CD8+ T cells, by exogenous stimuli, can precipitate late loss of islet allografts. Recipients were induced to accept intrahepatic islet allografts (islet 'acceptors') by short-term immunotherapy with donor-specific transfusion (DST) and anti-CD154 mAb. Following the establishment of stable long-term islet allograft function for 60-90 days, recipients were challenged with donor-matched hepatocellular allografts, which are known to activate (CD4-independent) CD8+ T cells. Allogeneic islets engrafted long-term were vulnerable to damage when challenged locally with donor-matched hepatocytes. Islet allograft loss was due to allospecific immune damage, which was CD8- but not CD4-dependent. Selection of specific immunotherapy to suppress both CD4- and CD8-dependent immune pathways at the time of transplant protects islet allografts from both early and late immune damage.

publication date

  • June 2008



  • Academic Article



  • eng

PubMed Central ID

  • PMC3081659

Digital Object Identifier (DOI)

  • 10.1111/j.1600-6143.2008.02219.x

PubMed ID

  • 18522544

Additional Document Info

start page

  • 1113

end page

  • 28


  • 8


  • 6