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CD70 Signaling Is Critical for CD28-Independent CD8+ T Cell-Mediated Alloimmune Responses In Vivo
| Content Provider | Scilit |
|---|---|
| Author | Yamada, Akira Salama, Alan D. Sho, Masayuki Najafian, Nader Ito, Toshiro Forman, John P. Kewalramani, Reshma Sandner, Sigrid Harada, Hiroshi Clarkson, Michael R. Mandelbrot, Didier A. Sharpe, Arlene H. Oshima, Hideo Yagita, Hideo Chalasani, Geetha Lakkis, Fadi G. Auchincloss, Hugh Sayegh, Mohamed H. |
| Copyright Year | 2005 |
| Description | 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. |
| Ending Page | 1364 |
| Page Count | 8 |
| Starting Page | 1357 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.174.3.1357 |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/174/3/1357.full.pdf |
| Journal | The Journal of Immunology |
| Issue Number | 3 |
| Volume Number | 174 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2005-02-01 |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
