The CD4+ CD52 low T Cells Contributes to the Development of Systemic Lupus Erythematosus through the CCR8/TARC Pathways

Objective: CD52 is a cell-surface glycoprotein that is widely expressed in lymphocytes. CD4+CD52high T cells inhibit the activation of CD4+CD52low T cells through the release of cell-surface CD52. The role of the immune regulation of these cells in systemic lupus erythematosus (SLE) is unknown. Methods: Blood samples obtained from SLE patients, rheumatoid arthritis (RA) patients and 33 healthy controls (HC). The expressions of CD4+CD52high T cells and CD4+CD52low T cells were analyzed by flow cytometry. To determine the genetic characteristics of these cells from SLE, we performed cDNA microarrays and examined the function of the genes in in-vitro. Results: The expression of CD4+CD52low T cells in the SLE was significantly higher than HC and non-SLE and its expression were positively correlated with SLEDAI, anti-ds-DNA antibodies and IgG. The population of circulating follicular helper like T cells (Tfh like cells) were increased in SLE and its expression was positively correlated with CD4+CD52low T cells. The microarray analysis revealed that the expression of chemokine receptor 8 (CCR8) is increased in CD4+CD52low T cells. In addition, in vitro experiments using CD4 T cells from patients with SLE showed that thymus and activation-regulated chemokine (TARC), known as a ligand of CCR8, induced the conversion of CD4+CD52high T cells into CD4+CD52low T cells. Conclusion: Our data suggest that increased CD4+CD52low T cells along with increased Tfh like cells are involved in the pathogenic autoantibodies production and that TRAC may contributes to the development of SLE via an aberrant induction of CD4+CD52low T cells. CD4+ CD52low T cells and CD4+ CD52high T cells from five SLE patients were sorted by sorting flow cytometry. The expression of messenger RNA from each populations was analyzed by microarray analysis.