THU0244 The role of stem cell-like memory t cells in systemic lupus erythematosus
Authors: YJ Lee, H Kwon, EB Lee
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The stem cell-like memory T (Tscm) cell, a special subset of memory T cell, has a potential to self-renew and differentiate into wide spectrum of T cells<sup>1</sup>. However, the role of Tscm in autoimmune disease such as systemic lupus erythematosus (SLE) remains to be unknown. <h3>Objectives</h3> To investigate the levels of Tscm cells in SLE patients compared with healthy controls and to understand the functional characteristics of the Tscm cells from SLE patients. <h3>Methods</h3> Fifty two SLE patients and 57 healthy controls (HCs) were enrolled. To detect Tscm cells which are designated as CD3<sup>+</sup> CD4<sup>+</sup>/CD8<sup>+</sup> CD45RO<sup>-</sup> CCR7<sup>+</sup> CD62L<sup>+</sup> CD45RA<sup>+</sup> CD27<sup>+</sup> CD28<sup>+</sup> CD127<sup>+</sup> CD122<sup>+</sup> CD95<sup>hi</sup>, flow cytometry was performed after staining peripheral blood mononuclear cells (PBMCs, 1x10<sup>7</sup> cells/mL) with fluorescence-conjugated antibodies. To ascertain the differentiation ability of Tscm cells, different subsets of T cells including naïve-like T, central memory T, effector memory T and follicular helper T cells (Tfh) were evaluated after stimulating the isolated Tscm cells with anti-CD3/CD28 antibodies for 6 days. To investigate the function of the Tfh cells derived from Tscm cells, secreted IgG antibodies were measured from the supernatants by ELISA after incubating Tfh –containing differentiated Tscm cells with autologous B cells and SEB for 6 days. <h3>Results</h3> Among the naive-like T (CD3<sup>+</sup> CD4<sup>+</sup> CCR7<sup>+</sup> CD45RO<sup>-</sup> CD45RA<sup>+</sup> CD62L<sup>+</sup>) cells, the proportion of CD4<sup>+</sup> and CD8<sup>+</sup> Tscm cells was significantly higher in SLE patients than HCs (for CD4<sup>+</sup> T cells, 2.29±0.22 (SLE) vs 1.11±0.13 (HC), p-value≦0.001; for CD8<sup>+</sup> T cells, 5.36±0.63 (SLE) vs 3.41±0.44 (HC), p-value=0.013). Among the total CD4<sup>+</sup> T cells, the ratio of Tscm to CD4<sup>+</sup> T cells was higher in SLE patients than in healthy controls (0.63±0.10 (SLE) vs 0.40±0.04 (HC), p-value=0.035) (Fig 1). SLE and HC Tscm cells could differentiate into naive-like T, central memory T, effector memory T cells and renewed themselves in response to α-CD3/CD28 stimuli. In addition, in response to the same stimuli, SLE Tscm cells could differentiate into more Tfh cells than HC Tscm cells could (for CXCR5<sup>+</sup> ICOS<sup>+</sup> PD-1<sup>+</sup> cells in CD4<sup>+</sup> T cells, 9.30% (SLE) vs 5.41% (HC) and for Bcl-6<sup>+</sup> cells in CD4<sup>+</sup> T cells, 34.29% (SLE) vs 19.20% (HC)). Tscm-derived Tfh cells could help B cells produce antibodies <i>in vitro</i> (12007.81±4457.54 (SLE) vs 2082.18±517.82 (HC)). <h3>Conclusions</h3> Proportions of Tscm cells among T cells is increased in SLE patients compared with HCs and the Tscm cells may help maintain SLE by its ability to differentiate into Tfh cells. <h3>References</h3> Luca Gattinoni et al, A human memory T cell subset with stem cell-like properties. Nature Medicine, 2011, 17: 1290-U325. <h3>Disclosure of Interest</h3> None declared