Autoreactive CD8+ T Cell Clones Producing Immune Suppressive Lymphokines IL-10 and Interferon-γ

Highly purified CD8+ T cells were stimulated repeatedly by syngeneic irradiated spleen cells. From separate cloning experiments, we succeeded in isolating two CD8+> clones, 4B4 and D2, which proliferated in response to autologous antigen-presenting cells (APC) completely in the absence of fetal calf serum. A T cell proliferation assay, using congenic strains of mice, indicates that both autoreactive clones were restricted to self-Db molecules. Our study is the first report of establishing murine autoreactive CD8+ clones restricted to self MHC class I molecules. To assess the immune suppressive activity of each autoreactive clone, we measured the production of IL-10 and interferon-γ, which have specific immune suppressive activity toward type 1 helper T cell (Th1) proliferation and IgE synthesis, respectively. In response to autologous APC, both D2 and 4B4 produced considerable amounts of interferon-γ and a low but significant level of IL-10. Each supernatant of D2 and 4B4 significantly suppressed IgE synthesis. These results strongly suggest the existence of CD8+ autoreactive T cells with immune suppresive activity.