Autoreactive CD8+ T cell clones producing immune suppressive lymphokines IL-10 and interferon-gamma.
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 strain 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-gamma, 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-gamma 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 suppressive activity.
Hisatsune
T
T
Department of Agricultural Chemistry, University of Tokyo, Japan.
Nishijima
K
K
Minai
Y
Y
Kohyama
M
M
Kaminogawa
S
S
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015551:Autoimmunity; D016827:CD8 Antigens; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016827:CD8 Antigens; D016753:Interleukin-10; D007371:Interferon-gamma