AUTOREACTIVE CD8(-CELL CLONES PRODUCING IMMUNE SUPPRESSIVE LYMPHOKINES IL-10 AND INTERFERON-GAMMA() T)

Highly purified CD8(+) T cells were stimulated repeatedly by syngeneic irradiated spleen cells. From separate cloning experiments, we succee ded in isolating two CD8(+) clones, 4B4 and D2, which proliferated in response to autologous antigen-presenting cells (APC) completely in th e absence of fetal calf serum. A T cell proliferation assay, using con genic strains of mice, indicates that both autoreactive clones were re stricted to self-D-b molecules. Our study is the first report of estab lishing murine autoreactive CD8(+) clones restricted to self MHC class I molecules. To assess the immune suppressive activity of each autore active done, we measured the production of IL-10 and interferon-gamma, which have specific immune suppressive activity toward type 1 helper T cell (Thl) proliferation and IgE synthesis, respectively. In respons e to autologous APC, both D2 and 4B4 produced considerable amounts of interferon-gamma and a low but significant level of IL-10. Each supern atant of D2 and 4B4 significantly suppressed IgE synthesis. These resu lts strongly suggest the existence of CD8(+) autoreactive T cells with immune suppressive activity. (C) 1994 Academic Press, Inc.