CD8+CD44+Ly49+ T regulatory cells were induced by CD4+ T cells which were activated by MHC class II-restricted peptide. CD8+CD44+Ly49+ T regulatory cells have a cross-suppressive activity on responding CD4+T cell. CD8+CD44+Ly49+ T regulatory cells suppress the proliferation and activation of responding CD4+ T cell in a cytotoxicity-dependent manner.