Increased Apoptosis and Compromised Suppressive Capacity of Regulatory T Cells in Primary Sjögren’s Syndrome

Min Feng¹, Xiangcong Zhao ¹ and Jing Luo ¹, ¹the second hospital of shanxi medical university, Taiyuan, China (People's Republic)

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Apoptosis, regulatory T cells and primary Sjögren’s syndrome, suppressive function

Session Information

Date: Tuesday, November 12, 2019

Title: Sjögrenʼs Syndrome – Basic & Clinical Science Poster I

Session Type: Poster Session (Tuesday)

Session Time: 9:00AM-11:00AM

Background/Purpose: To investigate the apoptosis and suppressive function of regulatory T cells (Tregs) in primary Sjögren’s syndrome (pSS), and the effect of low-dose IL-2 on apoptosis of Tregs.

Methods: Apoptosis of Tregs and effector T (Teff) cells were measured by staining with Annexin V and 7-amino-actinomycin D (7-AAD) in 54 female patients with pSS and 25 aged-matched female healthy controls (HCs) using flow cytometry. The function of Tregs was evaluated by the suppressive capacity to autologous CD4⁺CD25^– responder T (Tresp) cells expansion and was expressed as the proliferation of Tresp cells. The apoptosis degree of 13 pSS after the administration of low-dose IL-2 was also analyzed.

Results: Defect of number (P=0.030) and percentage (P=0.004) of Tregs was observed in pSS. Tregs was more sensitive to apoptosis than Teff cells, and apoptosis degree of Tregs was parallel to disease activity. Functional assay showed a compromised suppression for Tresp proliferation. The administration of low-dose IL-2 reduced the apoptitic rate of Tregs and Teff cells. Furthermore, serum concentrations of interleukin-6 (IL-6), IL-10, IL-17, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were positively associated with early apoptotic Tregs and Teff cells, but with late apoptotic Teff cells negatively. In addition, Cystatin C, α1 microglobulin and β2 microglobulin could contribute to the early apoptosis of Tregs (r=0.553, P=0.001; r=0.537, P=0.004; r=0.552, P=0.001) and Teff cells (r=0.534, P=0.001; r=0.560, P=0.002; r=0.401, P=0.019).

Conclusion: Aberrant increased apoptosis and impaired function of Tregs may partially contribute to the immune imbalance, leading to the onset of pSS. And multiple up-regulated cytokines, cystatin C, α1 microglobulin and β2 microglobulin were responsible for the increased sensitivity to apoptosis of Tregs. Low-dose IL-2 could decrease the sensitivity to apoptosis of Tregs and alleviate disease activity.

Table 1. Demographic and serological characteristics of patients and controls

Figure 1: -a- Apoptosis of Tregs and effector T -Teff- cells in pSS and HCs. The left two scatter plots referred to the left Y-axis, and the right two scatter plots referred to the right Y-axis. Comparisons of live, early apoptotic, late apoptotic/necrotic, and total apoptotic Tregs and Teff cells between pSS and HCs. And comparisons of early apoptotic, late apoptotic, and total apoptotic Tregs and Teff cells in pSS and HCs, respectively. -b- Comparisons of rate of live, early apoptosis, late apoptotis, total apoptosis of Treg and Teff cells in low-activity -ESSDAI<5, n=22-, medium-activity -5≤ESSDAI≤13, n=29- and high-activity -ESSDAI≥14, n=3- in pSS, respectively. -c- Apoptosis of Tregs and Teff cells in response to low-dose IL-2 administration in pSS was shown. Rate of live cells referred to the left Y-axis, and the proportions of early, late and total apoptotic cells referred to the right Y-axis.

Figure 2. The suppressive function of Tregs for Tresp cells proliferation in different Tresp/Treg ratio -1:0, 1:1, 2:1, 4:1 and 8:1- was examined by flow cytometry. -a- Suppressive capacity of Tregs was in a Tresp/Treg ratio-dependent manner. Data were presented as median -Q25, Q75- and were analyzed by the Independent-samples Kruskal-Wallis test one-way ANOVA. -b- Suppressive capacity of Tregs and the proliferation of Tresp cells themselves were compromised in pSS compared with healthy controls -HCs-. Data were presented as median -Q25, Q75- and were compared by Mann-Whitney U-test. *P<0.05.

Disclosure: M. Feng, None; X. Zhao, None; J. Luo, None.

To cite this abstract in AMA style:

Feng M, Zhao X, Luo J. Increased Apoptosis and Compromised Suppressive Capacity of Regulatory T Cells in Primary Sjögren’s Syndrome [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/increased-apoptosis-and-compromised-suppressive-capacity-of-regulatory-t-cells-in-primary-sjogrens-syndrome/. Accessed .

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