AB0175 ABSOLUTE REDUCTION OF PERIPHERAL CD4+CD25+FOXP3+T REGULATORY CELLS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Xiaoqing Liu, Yanan Duan, Nalin Lai, Gaiqin Chai
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> T lymphocytes are important contributors to systematic lupus erythematosus (SLE). Regulatory T (Treg) cells, with the capacity to suppress immune responses, effector T cells (Teff), which promote inflammation, have been intensively studied in recent years. However, previous reports describing the respective changes of Treg and Teff, especially T helper cells (Th17) in SLE patients were controversial. Here, we investigated both absolute number and percentage of CD4+CD25+Foxp3+Treg (CD4Treg) cells and effector cells on a large scale and the role of low-dose interleukin-2 (IL-2) in SLE. <h3>Objectives</h3> To investigate both absolute number and percentage of CD4+CD25+Foxp3+Treg (CD4Treg) cells and effector cells on a large scale and the role of low-dose interleukin-2 (IL-2) in SLE. <h3>Methods</h3> Two hundred and thirty-five SLE patients (219 women and 16 men), with mean age of 37.80 ± 14.00 years, were enrolled. The absolute count and percentage of subpopulation of peripheral blood (PB) lymphocyte in these patients were measured by flow cytometry combined with internal microsphere standard. And low-dose IL-2 was used among 127 patients at a dosage of fifty WIU every day for five days. Immunological and clinical assessments were performed again at the end of IL-2 treatment. Ninety healthy volunteers, matched for patients' age and gender, were also included for the estimation of lymphocyte subsets. <h3>Results</h3> As compared to healthy controls (median of Treg cells: 33.09 cells/ul), the absolute number of circulating CD4Treg cells were significantly decreased in SLE patients (median: 15.49 cells/ul, P&lt;0.001). The median ratios of Th17/Treg cells in patients were greatly higher than those of healthy volunteers [0.42 (0.19, 0.88) vs. 0.21 (0.15, 0.34), P&lt;0.001], while there was not significantly different in peripheral Th17 cell between two groups. Besides, Th1, Th2, CD8+T, B cells and their respective ratios to Treg cells were like that of Th17 cells as well. Moreover, CD4Treg cells were negatively correlated with ESR and SLEDAI score (r=-0.198, P=0.01; r=-0.25, P=0.002). While no obvious correlation was seen between Th17 cells and SLEDAI score. After IL-2 therapy in SLE, there was a four-fold increase in circulating CD4Treg cells [43.73 (24.08, 74.22) vs. 11.95 (7.51, 20.34), P&lt;0.001], whereas Th17 cells were increased slightly. The ratio of Th17/Tregs was decreased significantly in patients with IL-2 treatment [0.19 (0.09, 0.41) vs. 0.52 (0.23, 0.95), P&lt;0.001], tended to balance and had no difference with healthy individual (P=0.275). Similarly, there were same trends in Th1, Th2, CD8+T, B and NK cells. <h3>Conclusion</h3> The reduction of CD4Tregs but not the elevation of effector cells may be the major reason for imbalance of Teff/Treg, indicating that SLE is an autoimmune disease triggered by the defect of immunotolerance. More importantly, low-dose IL-2 might promote the proliferation of various lymphocyte subpopulation, and mainly modulated the abundance and immunosuppression activity of Tregs, which effectively induced autoimmune tolerance and further improved clinical symptoms. <h3>References</h3> [1] Bonelli M, Goschl L, Bluml S, et al. (2014) CD4+CD25-Foxp3+T cells: a marker for lupus nephritis?Arthritis Research &amp; Therapy. 16: R104. [2] M Miyara, G Gorochov, M Ehrenstein, et al. (2011) Human FoxP3+ regulatory T cells in systemic autoimmune diseases. Autoimmunity Reviews. 10(12): 744-55. [3] Żabińska M, Krajewska M, Kościelska-Kasprzak K, et al. (2016) CD4(+)CD25(+) CD127(-) and CD4(+)CD25(+)Foxp3(+) Regulatory T Cell Subsets in Mediating Autoimmune Reactivity in Systemic Lupus Erythematosus Patients. Arch Immunol Ther Exp (Warsz). 64(5): 399-407. <h3>Disclosure of Interests</h3> None declared