Qa-1–dependent CD8⁺ T cells are involved in the establishment and maintenance of peripheral self tolerance to HEL in HEL Tg mice. (A) The unresponsiveness to HEL in HEL high Tg mice could be broken by treatment with anti-CD8 and anti–Qa-1 mAbs. HEL immunization and in vivo mAb treatment were performed and CD4⁺ T cells were purified from pooled draining lymph node cells from different groups of mice and assayed in a T cell proliferation assay as described in Methods. Data are representative of 4 separate experiments with 2–4 mice per group. (B) CD8⁺ T cells regulate immune response to self antigen HEL in HEL low Tg mice. Experiments were performed as described in Methods. Data are representative of 6 separate experiments with 2–4 mice per group. (C) CD8⁺ T cells downregulate the primary immune responses to HEL in HEL low Tg mice when adoptively transferred. CD8⁺ T cells were injected i.v. into recipient mice, and the mice were immunized with HEL 1 day later. The CD4⁺ T cells were isolated from pooled lymph node cells of recipient mice 7–9 days after the immunization, and T cell proliferation assays were performed. Data are representative of 4 separate experiments with 2–4 mice per group. Control, no transfer; n/LTg, CD8⁺ T cells transferred from naive HEL low Tg mice; HEL/LTg, CD8⁺ T cells transferred from 2– HEL-immunized HEL low Tg mice; n/HTg, CD8⁺ T cells transferred from naive HEL high Tg mice; HEL/HTg, CD8⁺ T cells transferred from 1– HEL-immunized HEL high Tg mice. ³HTdr, ³H-thymidine.