GVHD-associated autoimmunity is due to the absence of appropriate T-cell regulation. Lethally irradiated (900 cGy) B10.BR mice received transplants of TCD B6 BM (10 × 10⁶) plus 2 × 10⁶ B6 spleen cells. Mice were killed 21 days after transplantation, and spleen cells (adjusted to yield a T-cell dose of 10⁶ T cells per animal) were transferred into nonirradiated B6 Rag mice alone (n = 3) or together with 19 × 10⁶ purified B cells (n = 9) from normal B6 animals. In subsequent experiments, lethally irradiated (900 cGy) Balb/c mice received transplants of TCD B6 BM (10 × 10⁶) plus 3-4 × 10⁵ B6 spleen cells. At 20 to 23 days after BMT, mice were killed, and spleen cells (adjusted to yield 0.5-1 × 10⁶ T cells) were transferred alone (n = 8-21 mice/group) or together with an equivalent number of CD4⁺ plus CD8⁺ (n = 11), CD8⁺ (n = 21), or CD4⁺ T cells (n = 8) from B6.PL (Thy1.1⁺) animals into nonirradiated B6 Rag animals. Data are presented as means plus or minus SEM. (A) Overall pathology score of mice that received transplants of GVHD spleen cells alone (■) or together with the specified population of purified B or T cells from normal B6 or B6.PL mice (□). (B) Absolute number of Thy 1.2⁺ T cells in the spleens of mice that received transplants of GVHD spleen cells alone (■) or together with either CD3⁺, CD8⁺, or CD4⁺ T cells from normal B6.PL animals (□). (C) Absolute number of Thy 1.2⁺ (■) and Thy1.1⁺ (□) T cells in the spleens of mice that received transplants of GVHD spleen cells and either CD3⁺, CD8⁺, or CD4⁺ T cells from normal B6.PL animals. (D) Absolute number of Gr-1⁺ Mac-1⁺ cells in the spleens of mice that received transplants of GVHD spleen cells alone (■) or together with either purified CD8⁺ or CD4⁺ T cells (□) from normal B6.PL mice. Statistics: *P < .05; **P < .01.