Lethal autoimmune T cells induced by a perinatal blockade of costimulatory molecules B7-1 and B7-2. C57BL/6j mice were treated with a mixture of anti–B7-1 and anti–B7-2, or rat and hamster IgG as control, from day 16 of pregnancy to day 10 after birth. 3 wk after birth, CD4-enriched thymocytes were prepared from anti–B7-treated and control IgG-treated male mice, respectively, and injected in high (hi, 2 × 108 per mouse) or low (lo, 2 × 107 per mouse) doses into 14-d-old syngeneic RAG-1−/− mice. Purified spleen T cells (2 × 107 per mouse) were isolated from both groups of mice and were adoptively transferred intraperitoneally into 2-wk-old, syngeneic nu+/nu+ mice. The recipients were monitored every day, and dead or moribund mice were subject to necropsies. (a) Rapid onset of fatal attack by either CD4-enriched thymocytes (top, n = 5) or spleen T cells (bottom, n = 5 for anti–B7-treated group; n = 4 for control IgG-treated group). (b) Histology of lung and heart sections from a RAG-1−/− recipient (upper left), and a pancreas, a muscle (M) and nerve (N) sections of a nu+/nu+ recipient (upper right). The organs from recipients of T cells from control Ig-treated mice were harvested 2 mo after adoptive transfer (bottom). The data shown are representative of two independent experiments.