%0 Journal Article %J J Immunol %D 2001 %T Rejection of mouse cardiac allografts by costimulation in trans. %A Mandelbrot, D A %A Kishimoto, K %A Auchincloss, H %A Sharpe, A. H. %A Sayegh, M H %K Animals %K Antigen-Presenting Cells %K Antigens, CD %K Antigens, CD4 %K Antigens, CD80 %K Antigens, CD86 %K CD4-Positive T-Lymphocytes %K CD8-Positive T-Lymphocytes %K Cells, Cultured %K Graft Rejection %K Heart Transplantation %K Histocompatibility Antigens Class II %K Lymphocyte Activation %K Lymphocyte Culture Test, Mixed %K Male %K Membrane Glycoproteins %K Mice %K Mice, Inbred BALB C %K Mice, Inbred C57BL %K Mice, Knockout %K Transplantation, Homologous %X The activation of T cells by B7 costimulation in trans has been demonstrated in vitro, but the in vivo relevance is unknown. To study costimulation in trans of CD4(+) T cells in vivo, we performed cardiac transplants from B7-1/B7-2-deficient mice to recipients that do not express MHC class II molecules on peripheral APCs, but do have functional CD4(+) T cells (II(-)/4(+) mice). This model restricts the B7-dependent activation of CD4(+) T cells to costimulation in trans and excludes any contribution from indirect Ag presentation. We find that II(-)/4(+) recipients reject B7-deficient grafts as rapidly as wild-type grafts, suggesting that costimulation in trans can mediate rejection as potently as costimulation in cis. Treatment of II(-)/4(+) recipients of B7-deficient grafts with depleting Abs to CD4 or CD8 demonstrates that indirect Ag presentation to CD8(+) cells does not significantly contribute to rejection. This is the first demonstration that costimulation in trans can mediate an immune response in vivo and has important therapeutic implications. %B J Immunol %V 167 %P 1174-8 %8 2001 Aug 1 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/11466331?dopt=Abstract