Objective Accelerated atherosclerosis is a major source of morbidity in systemic lupus erythematosus (SLE). However, the cause of SLE-accelerated atherosclerosis remains unclear.

Methods CD4⁺ T cells from C57/Bl/6 (B6) or SLE-susceptible B6.Sle1.2.3 (B6.SLE) mice were transferred into LDLr^−/−, Rag^−/− mice. T cells were examined for cytokine production and expression of interleukin-10 receptor (IL-10R) and functional markers. T cells were isolated based on FoxP3^GFP expression and transferred to LDLr^−/−, Rag^−/− mice to establish a role for B6.SLE effector T cells (T_eff) in atherosclerosis.

Results Mice receiving whole B6.SLE CD4⁺ T cells displayed no other SLE phenotype; however, atherosclerosis was increased nearly 40%. We noted dysregulated IL-17 production and reduced frequency of IL-10R expression by B6.SLE regulatory T cells (T_reg). Functional assays indicated resistance of B6.SLE T_eff to suppression by both B6.SLE and B6 T_reg. Transfer experiments with CD4⁺FoxP3⁻ T_eff and CD4⁺FoxP3⁺ T_reg from B6.SLE and B6 mice, respectively, resulted in increased atherosclerosis compared with B6 T_eff and T_reg recipients. T_reg isolated from mice receiving B6.SLE T_eff with B6 T_reg had increased production of IL-17 and fewer expressed IL-10R compared with B6 T_eff and T_reg transfer.

Conclusions Transfer of B6.SLE T_eff to LDLr^−/−, Rag^−/− mice results in accelerated atherosclerosis independent of the source of T_reg. In addition, the presence of B6.SLE T_eff resulted in more IL-17-producing T_reg and fewer expressing IL-10R, suggesting that B6.SLE T_eff may mediate phenotypic changes in T_reg. To our knowledge, this is the first study to provide direct evidence of the role of B6.SLE T_eff in accelerating atherosclerosis through resistance to T_reg suppression.