The immune system includes a subpopulation of CD8⁺ T cells equipped to inhibit the expansion of follicular T helper (T_FH) cells, resulting in suppression of autoantibody production and associated lupus-like disease. These CD8⁺ T regulatory (Treg) cells recognize Qa-1/peptide complexes on target T_FH cells and depend on the IL-15 cytokine for development and function. Here we show that these CD8⁺ Treg cells express a triad of surface receptors—CD44, CD122, and the class I MHC receptor Ly49—and account for <5% of CD8⁺ T cells. Moreover, the development of systemic lupus erythematosus-like disease in B6-Yaa mutant mice is associated with a pronounced defect in CD8⁺ Treg cell activity, suggesting that this regulatory subset may represent an effective therapeutic approach to systemic lupus erythematosus-like autoimmune disease.