Background/Purpose: CD52 is a cell-surface glycoprotein that is widely expressed in lymphocytes, monocytes and eosinophils. CD4⁺CD52^high T cells inhibit the activation of CD4⁺CD52^low T cells through the release of cell-surface CD52. Soluble CD52, which is cleaved from CD4⁺CD52^high T cells, works as a ligand of siglec-10 on CD4⁺CD52^low T cells (1). CD4⁺CD52^high T cells were reported as distinct population from conventional regulatory T cells. The role of the immune regulation of these cells in systemic lupus erythematosus (SLE) is unknown. We evaluated the CD4⁺CD52⁺ T cells in the human peripheral blood mononuclear cells (PBMCs) of SLE patients and clarified their roles in the pathogenesis of SLE.

Methods: We isolated the PBMCs of 58 SLE patients, 22 non-SLE patients (19 with rheumatoid arthritis, 3 with mixed connective-tissue disease) and 33 healthy controls (HCs). The expressions of CD4⁺CD52^high T cells and CD4⁺CD52^low T cells were analyzed by flow cytometry. We also analyzed the correlations with clinical parameters including SLEDAI, anti-ds-DNA antibodies and complement. We then analyzed circulating follicular helper like T cells (Tfh like cells) identified as CD4⁺CXCR5^highICOS^highPD-1^high and plasmablast identified as CD3^–CD19⁺CD38⁺CD27⁺. To determine the genetic characteristics of CD4⁺CD52^low@and CD4⁺CD52^high T cells from SLE, we performed cDNA microarrays (SurePrint G3 Human GE 8x60K) and examined the function of the genes in in-vitro.

Results: We found that the expression of CD4⁺CD52^low T cells in the SLE was significantly higher than HC and non-SLE. The expression of CD4⁺CD52^low T cells of the SLE were positively correlated with SLEDAI, anti-ds-DNA antibodies and IgG. The population of Tfh like cells were increased in SLE and its expression was positively correlated with CD4⁺CD52^low T cells. The microarray analysis revealed that the expression of chemokine receptor 8 (CCR8) is significantly increased in CD4⁺CD52^low 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⁺CD52^high T cells into CD4⁺CD52^low T cells.

Conclusion: Collectively, our data suggest that increased CD4⁺CD52^low 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⁺CD52^low cells. References@1DNat Immunol. 2013: 14:741-8.