| First Author | Yamada A | Year | 2005 |
| Journal | J Immunol | Volume | 174 |
| Issue | 3 | Pages | 1357-64 |
| PubMed ID | 15661893 | Mgi Jnum | J:136519 |
| Mgi Id | MGI:3796412 | Doi | 10.4049/jimmunol.174.3.1357 |
| Citation | Yamada A, et al. (2005) CD70 signaling is critical for CD28-independent CD8+ T cell-mediated alloimmune responses in vivo. J Immunol 174(3):1357-64 |
| abstractText | The inability to reproducibly induce robust and durable transplant tolerance using CD28-B7 pathway blockade is in part related to the persistence of alloreactive effector/memory CD8(+) T cells that are less dependent on this pathway for their cellular activation. We studied the role of the novel T cell costimulatory pathway, CD27-CD70, in alloimmunity in the presence and absence of CD28-B7 signaling. CD70 blockade prolonged survival of fully mismatched vascularized cardiac allografts in wild-type murine recipients, and in CD28-deficient mice induced long-term survival while significantly preventing the development of chronic allograft vasculopathy. CD70 blockade had little effect on CD4(+) T cell function but prevented CD8(+) T cell-mediated rejection, inhibited the proliferation and activation of effector CD8(+) T cells, and diminished the expansion of effector and memory CD8(+) T cells in vivo. Thus, the CD27-CD70 pathway is critical for CD28-independent effector/memory CD8(+) alloreactive T cell activation in vivo. These novel findings have important implications for the development of transplantation tolerance-inducing strategies in primates and humans, in which CD8(+) T cell depletion is currently mandatory. |
