CD4⁺ CD52^lo T-cell expression contributes to the development of systemic lupus erythematosus

The cell-surface glycoprotein CD52 is widely expressed in lymphocytes. CD4⁺CD52^hi T cells are functioning suppressor CD4⁺T cells. We investigated the role of the immune regulation of CD4⁺CD52 T cells in systemic lupus erythematosus (SLE). CD4⁺CD52^lo T cells were increased in SLE patients, in positive correlation with SLEDAI, anti-ds-DNA antibody, and IgG concentration. Circulating follicular helper-like T cells (Tfh-like cells) were also increased in SLE, in positive correlation with CD4⁺CD52^lo T cells. Chemokine receptor 8 (CCR8) expression in CD4⁺CD52^lo T cells was increased. In vitro experiments using CD4 T cells of SLE patients showed that thymus and activation-regulated chemokine (TARC), a ligand of CCR8, contributed to the development of CD4⁺CD52^hi T cells into CD4⁺CD52^lo T cells. Our findings suggest that CD4+CD52lo T-cell upregulation is involved in the production of pathogens by autoantibodies, and TARC may contribute to the development of SLE through an aberrant induction of CD4⁺CD52^lo T cells.