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AB0180 The Role of Immune Regulation of CD4+CD52High T Cells in Systemic Lupus Erythematosus
  1. M. Umeda1,
  2. T. Koga1,
  3. K. Ichinose1,
  4. S. Tsuji1,
  5. S. Fukui1,
  6. A. Nishino1,
  7. Y. Nakashima1,
  8. T. Suzuki1,
  9. Y. Horai1,
  10. Y. Hirai1,
  11. S.-Y. Kawashiri1,
  12. N. Iwamoto1,
  13. T. Aramaki2,
  14. M. Tamai1,
  15. H. Nakamura1,
  16. K. Yamamoto3,
  17. T. Origuchi4,
  18. Y. Ueki2,
  19. A. Kawakami1
  1. 1Department of Rheumatology, Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
  2. 2Department of Rheumatology, Sasebo Chuo Hospital
  3. 3Biomedical Research Support Center, Nagasaki University School of Medicine
  4. 4Depertment Rehabilitaion Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

Abstract

Background CD52 is a cell-surface glycoprotein that is widely expressed in lymphocytes, monocytes and eosinophils. The anti-CD52 antibody has been used to treat multiple autoimmune diseases, and its effectiveness has been reported [1]. 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 [2]. The role of the immune regulation of CD4+CD52high T cells in systemic lupus erythematosus (SLE) is unknown.

Objectives We evaluated the CD4+CD52high 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 33 SLE patients, 8 non-SLE patients (6 with rheumatoid arthritis, 2 with mixed connective-tissue disease) and 11 healthy controls (HCs). The expressions of CD4+CD25+CD127− T cells (Tregs), 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 antibody titer and complement titer. The soluble CD52 was also analyzed in an ELISA among the SLE and non-SLE patients and HCs.

Results No significant difference was found in the population of CD4+CD25+ CD127− cells among the groups. There was no correlation between Tregs and CD4+CD52high T cells in SLE. We found that the expression of CD4+CD52low T cells of the SLE group were significantly correlated with SLEDAI (p-value=0.0485, r=0.346096). The expression of CD4+CD52low T cells in the SLE patients with high-SLEDAI (6>) was significantly higher than HC (p=0.0011) and non-SLE (p=0.0034). Soluble CD52 measured by ELISA was found to be decreased in the SLE group versus the other groups (vs. HC: p=0.0011; vs. non-SLE: p=0.0142).

Conclusions Collectively, our data indicate that increased CD4+CD52low T cells and decreased soluble CD52 may contribute to the development of SLE. Our findings suggested that CD4+CD52high T cells are involved in autoimmune diseases with different functions of Tregs. The determination of CD4+CD52low may contribute to evaluations of SLE's disease activity and may help elucidate the mechanisms underlying SLE.

References

  1. Rao SP, Sancho J, Campos-Rivera J, Boutin PM, Severy PB, Weeden T, Shankara S, Roberts BL, Kaplan JM. Human peripheral blood mononuclear cells exhibit heterogeneous CD52 expression levels and show differential sensitivity to alemtuzumab-mediated cytolysis. PLoS One. 2012 Jun;7(6):e39416.

  2. Bandala-Sanchez E, Zhang Y, Reinwald S, Dromey JA, Lee BH, Qian J, Böhmer RM, Harrison LC. T cell regulation mediated by interaction of soluble CD52 with the inhibitory receptor Siglec-10. Nat Immunol. 2013 Jul;14(7):741-8.

Disclosure of Interest None declared

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