Seoul National University College of Medicine, Seoul, South Korea.
Arthritis Rheumatol. 2018 Sep;70(9):1459-1469. doi: 10.1002/art.40524. Epub 2018 Aug 2.
Stem cell-like memory T (Tscm) cells are long-lived memory T cells that have multipotent capacity to differentiate into different subsets. However, the role of Tscm cells in autoimmune diseases remains unclear. Here, we performed phenotypic studies to identify Tscm cells in patients experiencing systemic lupus erythematosus (SLE).
CD4+ and CD8+ Tscm cells were identified in SLE patients and healthy controls (HCs). In in vitro culture systems, CD4+ Tscm cells were induced to differentiate into subsets of T cells, including follicular helper T (Tfh) cells, and cytokine production patterns were assessed after stimulation. After confirming induction of transcription factors for Tfh cells, the capacity of CD4+ Tscm-derived Tfh cells to help B cells was analyzed by measuring antibody secretion.
The percentages of CD4+ and CD8+ Tscm cells among the naive CD4+/CD8+ or total CD4+ T cell populations were significantly higher in SLE patients than in HCs. Stimulated Tscm cells from SLE patients could replenish themselves and differentiate into other T lymphocyte subsets, including Tfh cells upon stimulation with T cell receptor. Production of T cell factor 1, which is an inducer of Tfh, was also increased. The differentiated Tfh cells increased antibody production by autologous B cells.
Taken together, these findings suggest that Tscm cells play a role in the pathogenesis of SLE by maintaining Tfh cells.
干细胞样记忆 T（Tscm）细胞是具有多能性分化为不同亚群能力的长寿记忆 T 细胞。然而，Tscm 细胞在自身免疫性疾病中的作用尚不清楚。在这里，我们进行了表型研究，以鉴定系统性红斑狼疮（SLE）患者中的 Tscm 细胞。
在 SLE 患者和健康对照者（HCs）中鉴定 CD4+和 CD8+Tscm 细胞。在体外培养系统中，诱导 CD4+Tscm 细胞分化为 T 细胞亚群，包括滤泡辅助 T（Tfh）细胞，并在刺激后评估细胞因子产生模式。在确认诱导 Tfh 细胞的转录因子后，通过测量抗体分泌来分析 CD4+Tscm 衍生的 Tfh 细胞帮助 B 细胞的能力。
与 HCs 相比，SLE 患者的幼稚 CD4+/CD8+或总 CD4+T 细胞群中 CD4+和 CD8+Tscm 细胞的百分比明显更高。刺激 SLE 患者的 Tscm 细胞可以在受到 T 细胞受体刺激时自我补充并分化为其他 T 淋巴细胞亚群，包括 Tfh 细胞。T 细胞因子 1（Tfh 的诱导剂）的产生也增加了。分化的 Tfh 细胞增加了自身 B 细胞的抗体产生。
综上所述，这些发现表明 Tscm 细胞通过维持 Tfh 细胞在 SLE 的发病机制中发挥作用。
