AB0037 The Characteristic of Cd4+Cd45Ra-Foxp3Low Cells in Patients with Systemic Sclerosis
Authors: N. Gao, M. Li, Q. Wang, Y. Hou, D. Xu, X. Zeng
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> 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<sup>+</sup>CD45RA<sup>+</sup>FoxP3<sup>low</sup> (FrI), CD4<sup>+</sup>CD45RA<sup>-</sup>FoxP3<sup>high</sup> (FrII), and CD4<sup>+</sup>CD45RA<sup>-</sup>FoxP3<sup>low</sup> (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. <h3>Objectives</h3> 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. <h3>Methods</h3> CD4+ T cells sorted by magnetic bead were stimulated with IL-6,IL-1βand TGF-βfor 120hr. The amounts of IL-17 and CD4<sup>+</sup>CD45RA<sup>-</sup>FoxP3<sup>low</sup> counts were assessed. <h3>Results</h3> (1) CD4+T cells stimulated by IL-6, IL-1, TGF-β in vitro could differentiate to more CD4<sup>+</sup>CD45RA<sup>-</sup>FoxP3<sup>low</sup>cells 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<sup>+</sup>CD45RA<sup>-</sup>FoxP3<sup>low</sup> 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 <h3>Conclusions</h3> CD4<sup>+</sup>CD45RA<sup>-</sup>FoxP3<sup>low</sup> (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<sup>+</sup>CD45RA<sup>-</sup>FoxP3<sup>low</sup> cells promots the pathophysiology and development of SSc. <h3>References</h3> Zuber JP, Spertini F (2006) Immunological basis of systemic sclerosis. Rheumatology (Oxford) 45 Suppl 3: iii23–25. Abraham DJ, Krieg T, Distler J, Distler O (2009) Overview of pathogenesis of systemic sclerosis. Rheumatology (Oxford) 48 Suppl 3: iii3–7. 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. Sakaguchi S, Miyara M, Costantino CM, Hafler DA (2010) FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10: 490–500. LeRoy EC, Medsger TA Jr (2001) Criteria for the classification of early systemic sclerosis. J Rheumatol 28: 1573–1576. <h3>Acknowledgements</h3> This study was supported by the Chinese National National High Technology Researchand Development Program, Ministry of Scienceand Technology (2012AA02A513). <h3>Disclosure of Interest</h3> None declared