Reduced regulatory effects of bone marrow-derived mesenchymal stem cells on activated T lymphocytes and Th1/Th2 cytokine secretion in children with aplastic anemia.

Autor: Guo, Xiaoping, Weng, Wenwen, Wang, Yuwen, Pan, Jin, Li, Sisi, Chen, Yuanyuan, Song, Hua, Zhang, Jingying, Xu, Weiqun, Xu, Xiaojun, Tang, Yongmin
Předmět:
Zdroj: Clinical & Experimental Medicine; Dec2023, Vol. 23 Issue 8, p4633-4646, 14p
Abstrakt: Acquired aplastic anemia (AA) is a recognized immune-mediated disorder and abnormally activated T lymphocyte-mediated bone marrow destruction is considered to be its main pathogenesis. Whether abnormal activation of T lymphocytes would also damage bone marrow-derived MSCs remains to be further studied. The aim of this study was to analyze the extent of T lymphocyte activation and the levels of Th1/Th2 cytokines of AA patients, and to explore the immunomodulatory effects of BM-MSCs on IL-2-stimulated T lymphocyte activation and cytokine production in vitro by means of transwell co-culture assay and flow cytometry measurement. The intermediate (CD25+) activated T cells were dominant in peripheral blood, while the early (CD69+) and late (HLA-DR+) activated T cells were predominant in bone marrow. Severe AA patients have an obviously higher proportion of CD3+CD8+CD69+ T cells than NSAA cases. The levels of IL-2 and IL-6 in AA patients were slightly elevated and INF-γ was mildly decreased in comparison with normal individuals. BM-MSCs derived from AA could not effectively inhibit the IL-2-induced activation of T cells with higher proportions of CD25+CD3+CD4+, CD69+CD3+CD4+ and CD25+CD3+CD8+ T cells after co-culture, and they showed a decreased ability to balance the Th1/Th2 cytokine production. Moreover, they had less robust osteogenic differentiation and more prone to adipogenic differentiation. We concluded that abnormally excessive T cell activation accompanied by abnormal cytokine secretion may impair the function of BM-MSCs in children with aplastic anemia. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index