Autoreactive CD4⁺ T cells that escape thymic negative selection cause GVHD only when peripheral regulatory mechanisms by T cells are eliminated. At 10 weeks after BMT, splenic CD4⁺ T cells (1 × 10⁷) isolated from [wt → wt] and [II^–/– → wt] chimeras were injected into either irradiated (6.5 Gy) or unirradiated wt mice (n = 5 or 6 per group). Survival after transfer (A) and pathology scores of the liver and small and large intestine at 6 weeks after transfer (B) (n = 3 per group) are shown. Results from 2 similar experiments are combined and represent mean ± SE. Survival (C) and clinical score (D) after adoptive transfer of CD4⁺ T cells from [II^–/– → wt] chimeras into lethally irradiated wt mice with or without cotransfer of splenic CD4^–CD8^– cells (non-T cells, 2 × 10⁷), CD4⁺ T cells (1 × 10⁷), 1 × 10⁷ CD8⁺ T cells (1 × 10⁷), or splenic CD4⁺ plus CD8⁺ T cells (2 × 10⁷) isolated from naive wt mice. (E) DP thymocytes were enumerated 5 weeks after transfer. UD indicates undetectable. *P < .05.