OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: Taken together, these findings suggest that Tscm cells play a role in the pathogenesis of SLE by maintaining Tfh cells.
OBJECTIVE: 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). METHODS:CD4+ and CD8+ Tscm cells were identified in SLEpatients 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. RESULTS: The percentages of CD4+ and CD8+ Tscm cells among the naive CD4+/CD8+ or total CD4+ T cell populations were significantly higher in SLEpatients than in HCs. Stimulated Tscm cells from SLEpatients 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. CONCLUSION: Taken together, these findings suggest that Tscm cells play a role in the pathogenesis of SLE by maintaining Tfh cells.
Authors: Maria Teresa Cencioni; Angela Genchi; Gavin Brittain; Thushan I de Silva; Basil Sharrack; John Andrew Snowden; Tobias Alexander; Raffaella Greco; Paolo A Muraro Journal: Front Immunol Date: 2022-02-01 Impact factor: 7.561
Authors: Nur Diyana Mohd Shukri; Aziz Farah Izati; Wan Syamimee Wan Ghazali; Che Maraina Che Hussin; Kah Keng Wong Journal: Front Immunol Date: 2021-06-04 Impact factor: 7.561
Authors: Lindsey E Padgett; Huy Q Dinh; Runpei Wu; Dalia E Gaddis; Daniel J Araujo; Holger Winkels; Anh Nguyen; Coleen A McNamara; Catherine C Hedrick Journal: Arterioscler Thromb Vasc Biol Date: 2020-10-15 Impact factor: 10.514