%0 Journal Article %J J Immunol %D 2001 %T CD28-independent costimulation of T cells in alloimmune responses. %A Yamada, A %A Kishimoto, K %A Dong, V M %A Ho, MS %A Salama, A D %A Anosova, N G %A Benichou, G %A Mandelbrot, D A %A Sharpe, A. H. %A Turka, L A %A Auchincloss, H %A Sayegh, M H %K Animals %K Antibodies, Blocking %K Antigens, CD %K Antigens, CD28 %K Antigens, CD80 %K Antigens, Differentiation %K CTLA-4 Antigen %K Graft Rejection %K Heart Transplantation %K Immune Sera %K Immunoconjugates %K Injections, Intraperitoneal %K Isoantigens %K Lymphocyte Activation %K Lymphocyte Culture Test, Mixed %K Mice %K Mice, Inbred BALB C %K Mice, Inbred C57BL %K Mice, Knockout %K Receptors, Antigen, T-Cell %K Signal Transduction %K T-Lymphocytes %X T cell costimulation by B7 molecules plays an important role in the regulation of alloimmune responses. Although both B7-1 and B7-2 bind CD28 and CTLA-4 on T cells, the role of B7-1 and B7-2 signaling through CTLA-4 in regulating alloimmune responses is incompletely understood. To address this question, we transplanted CD28-deficient mice with fully allogeneic vascularized cardiac allografts and studied the effect of selective blockade of B7-1 or B7-2. These mice reject their grafts by a mechanism that involves both CD4(+) and CD8(+) T cells. Blockade of CTLA-4 or B7-1 significantly accelerated graft rejection. In contrast, B7-2 blockade significantly prolonged allograft survival and, unexpectedly, reversed the acceleration of graft rejection caused by CTLA-4 blockade. Furthermore, B7-2 blockade prolonged graft survival in recipients that were both CD28 and CTLA-4 deficient. Our data indicate that B7-1 is the dominant ligand for CTLA-4-mediated down-regulation of alloimmune responses in vivo and suggest that B7-2 has an additional receptor other than CD28 and CTLA-4 to provide a positive costimulatory signal for T cells. %B J Immunol %V 167 %P 140-6 %8 2001 Jul 1 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/11418642?dopt=Abstract