Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: CD52 is a cell-surface glycoprotein that is widely expressed in lymphocytes, monocytes and eosinophils. CD4+CD52high T cells inhibit the activation of CD4+CD52low T cells through the release of cell-surface CD52. Soluble CD52, which is cleaved from CD4+CD52high T cells, works as a ligand of siglec-10 on CD4+CD52low T cells (1). CD4+CD52high 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+CD52high T cells and CD4+CD52low 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+CXCR5highICOShighPD-1high and plasmablast identified as CD3–CD19+CD38+CD27+. To determine the genetic characteristics of CD4+CD52low@and CD4+CD52high 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+CD52low T cells in the SLE was significantly higher than HC and non-SLE. The expression of CD4+CD52low 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+CD52low T cells. The microarray analysis revealed that the expression of chemokine receptor 8 (CCR8) is significantly 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: Collectively, 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 cells. References@1DNat Immunol. 2013: 14:741-8.
To cite this abstract in AMA style:Sato T, Umeda M, Koga T, Igawa T, Kurushima S, Takatani A, Shimizu T, Fukui S, Nishino A, Horai Y, Kawashiri S, Iwamoto N, Hirai Y, Tamai M, Nakamura H, Origuchi T, Kawakami A. The CD4+CD52low T Cell Contributes to the Development of Systemic Lupus Erythematosus through the CCR8/TARC Pathway [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/the-cd4cd52low-t-cell-contributes-to-the-development-of-systemic-lupus-erythematosus-through-the-ccr8tarc-pathway/. Accessed November 30, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-cd4cd52low-t-cell-contributes-to-the-development-of-systemic-lupus-erythematosus-through-the-ccr8tarc-pathway/