@article {542566, title = {CD70 signaling is critical for CD28-independent CD8+ T cell-mediated alloimmune responses in vivo.}, journal = {J Immunol}, volume = {174}, number = {3}, year = {2005}, month = {2005 Feb 1}, pages = {1357-64}, abstract = {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.}, keywords = {Acute Disease, Adoptive Transfer, Animals, Antibodies, Blocking, Antibodies, Monoclonal, Antigens, CD, Antigens, CD27, Antigens, CD28, Antigens, CD70, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Chronic Disease, Down-Regulation, Graft Rejection, Graft Survival, Heart Transplantation, Immunologic Memory, Isoantibodies, Killer Cells, Natural, Lymphocyte Activation, Membrane Proteins, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, Mutant Strains, Mice, Transgenic, Signal Transduction, T-Lymphocytes, Cytotoxic, Th1 Cells, Th2 Cells, Transplantation, Heterotopic, Up-Regulation}, issn = {0022-1767}, author = {Yamada, Akira and Salama, Alan D and Sho, Masayuki and Najafian, Nader and Ito, Toshiro and Forman, John P and Kewalramani, Reshma and Sandner, Sigrid and Harada, Hiroshi and Clarkson, Michael R and Mandelbrot, Didier A and Sharpe, Arlene H and Oshima, Hideo and Yagita, Hideo and Chalasani, Geetha and Lakkis, Fadi G and Auchincloss, Hugh and Sayegh, Mohamed H} }