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AB0037 The Characteristic of Cd4+Cd45Ra-Foxp3Low Cells in Patients with Systemic Sclerosis
  1. N. Gao,
  2. M. Li,
  3. Q. Wang,
  4. Y. Hou,
  5. D. Xu,
  6. X. Zeng
  1. peking union medical college hospital, Beijing, China

Abstract

Background Systemic sclerosis (SSc) is a heterogeneous autoimmune disease. Activated CD4+T cells elevation in the circulation and affected organs in SSc has been reported [1-2]. Recent studies reviewed immune suppression role deficiency of Treg in SSc [3]. Human CD4+FoxP3+T cells could be classified to three subtypes based on the expression of CD45RA: CD4+CD45RA+FoxP3low (FrI), CD4+CD45RA-FoxP3high (FrII), and CD4+CD45RA-FoxP3low (FrIII). We found that in SSc patients, the elevation in Treg cells was mainly due to an elevation in FrIII cell number, FrIII subtype is not suppressor for T cells, but can produce IL-17, and hence have Th17 potential [4]. It is reported that IL-17 plays an important role in SSc.

Objectives Twenty SSc patients without any previous treatment presenting to Peking Union Medical College Hospital (PUMCH) fulfilled the American College of Rheumatology (ACR) or LeRoy and Medsger criteria [5]. Twenty age and sex-matched healthy volunteers were enrolled as controls.

Methods CD4+ T cells sorted by magnetic bead were stimulated with IL-6,IL-1βand TGF-βfor 120hr. The amounts of IL-17 and CD4+CD45RA-FoxP3low counts were assessed.

Results (1) CD4+T cells stimulated by IL-6, IL-1, TGF-β in vitro could differentiate to more CD4+CD45RA-FoxP3lowcells either in patients with SSc (3.88±0.11 vs 2.94±0.19, P=0.006) or healthy controls (3.74±0.25 vs 2.71±0.21, P=0.003) compared with CD4+T cultured without these cytokines in vitro;

(2) CD4+CD45RA-FoxP3low cells could express more IL-17 either in patients with SSc (80.13±5.90 vs 58.39±2.84, P=0.005) or healthy controls (71.19±4.64 vs 48.05±4.06, P=0.003) after sorted CD4+T cells stimulated by IL-6, IL-1, TGF-β in vitro compared with CD4+T cultured without these cytokines

Conclusions CD4+CD45RA-FoxP3low (FrIII) cells shared the same characteristics with Th17 in secreting IL-17 and differentiation condition. As IL-17 plays an important role in the disease process of SSc, the elevated CD4+CD45RA-FoxP3low cells promots the pathophysiology and development of SSc.

References

  1. Zuber JP, Spertini F (2006) Immunological basis of systemic sclerosis. Rheumatology (Oxford) 45 Suppl 3: iii23–25.

  2. Abraham DJ, Krieg T, Distler J, Distler O (2009) Overview of pathogenesis of systemic sclerosis. Rheumatology (Oxford) 48 Suppl 3: iii3–7.

  3. Slobodin G, Ahmad MS, Rosner I, Peri R, Rozenbaum M, et al. (2010) Regulatory T cells (CD4(+)CD25(bright)FoxP3(+)) expansion in systemic sclerosis correlates with disease activity and severity. Cell Immunol 261: 77–80.

  4. Sakaguchi S, Miyara M, Costantino CM, Hafler DA (2010) FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10: 490–500.

  5. LeRoy EC, Medsger TA Jr (2001) Criteria for the classification of early systemic sclerosis. J Rheumatol 28: 1573–1576.

Acknowledgements This study was supported by the Chinese National

National High Technology Researchand Development Program, Ministry of Scienceand Technology (2012AA02A513).

Disclosure of Interest None declared

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