Background 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 cells¹. However, the role of Tscm in autoimmune disease such as systemic lupus erythematosus (SLE) remains to be unknown.

Objectives 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.

Methods Fifty two SLE patients and 57 healthy controls (HCs) were enrolled. To detect Tscm cells which are designated as CD3⁺ CD4⁺/CD8⁺ CD45RO^- CCR7⁺ CD62L⁺ CD45RA⁺ CD27⁺ CD28⁺ CD127⁺ CD122⁺ CD95^hi, flow cytometry was performed after staining peripheral blood mononuclear cells (PBMCs, 1x10⁷ 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.

Results Among the naive-like T (CD3⁺ CD4⁺ CCR7⁺ CD45RO^- CD45RA⁺ CD62L⁺) cells, the proportion of CD4⁺ and CD8⁺ Tscm cells was significantly higher in SLE patients than HCs (for CD4⁺ T cells, 2.29±0.22 (SLE) vs 1.11±0.13 (HC), p-value≦0.001; for CD8⁺ T cells, 5.36±0.63 (SLE) vs 3.41±0.44 (HC), p-value=0.013). Among the total CD4⁺ T cells, the ratio of Tscm to CD4⁺ 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⁺ ICOS⁺ PD-1⁺ cells in CD4⁺ T cells, 9.30% (SLE) vs 5.41% (HC) and for Bcl-6⁺ cells in CD4⁺ T cells, 34.29% (SLE) vs 19.20% (HC)). Tscm-derived Tfh cells could help B cells produce antibodies in vitro (12007.81±4457.54 (SLE) vs 2082.18±517.82 (HC)).

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Conclusions 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.

References

1. Luca Gattinoni et al, A human memory T cell subset with stem cell-like properties. Nature Medicine, 2011, 17: 1290-U325.

References

Disclosure of Interest None declared