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Title: [Inhibitory effects of tacrolimus on effector T cells from patients with severe aplastic anemia].
Author: Dong QE, Fu R, Liu CY, Ruan EB, Wang XM, Wang GJ, Qu W, Liu H, Wu YH, Song J, Xing LM, Guan J, Li LJ, Wang HQ, Shao ZH.
Journal: Zhonghua Yi Xue Za Zhi; 2013 May 28; 93(20):1541-5. PubMed ID: 24028719.
Abstract:
OBJECTIVE: To explore the inhibitory effects of tacrolimus (FK506) on effector T cells in vitro and examine the relationship between effector T cells and clinical features in patients with severe aplastic anemia (SAA) to elucidate its immune mechanism. METHODS: The CD8(+) HLA-DR(+) cells, sorted by immunomagnetic separation from bone marrow mononuclear cells (BMMNC) of 16 SAA patients, were cultured in different concentrations of interleukin-2 (IL-2) alone or with FK506 for 72 hours. The proliferation effect was measured with methyl thiazolyl tetrazolium (MTT) method. The T lymphocytes were sorted from the SAA patients by lymphocyte separation medium and cultured alone or with IL-2 or with FK506 or FK506 plus cyclosporin A (CsA) for 18 hours. The expression of tumor necrosis factor-β (TNF-β) in CD8(+) HLA-DR(+) T cells was analyzed by flow cytometry. The relationship between the expression of TNF-β and the clinical data, including percentages of reticulocyte and lymphocytes in peripheral blood cell count and ratio of CD4(+) T cells and CD8(+)T cells, was also analyzed. RESULTS: At the concentration of IL-2 greater than or equal to 20 U/ml, the cell proliferation (A values, 0.538 ± 0.142) were significantly higher than that in the blank culture hole (0.505 ± 0.153) (P < 0.05). The A values significantly decreased (0.386 ± 0.124) after the addition of FK506 (P < 0.05). Compared with control group, the expression of TNF-β was significantly higher in IL-2 group (73.36% ± 16.73% vs 66.61% ± 16.20%, P < 0.05), significantly lower in FK506 and FK506 plus CsA groups (P < 0.05). No significant differences existed between the FK506 and FK506 plus CsA groups (47.78% ± 20.09% and 42.23% ± 21.35%, P > 0.05). The expression of TNF-β in SAA was negatively correlated with the percentage of reticulocyte and the ratio of CD4(+) T cell and CD8(+) T cell, positively correlated with the percentage of lymphocyte in peripheral blood count (r = -0.86, -0.90, 0.77, all P < 0.05). CONCLUSIONS: IL-2 can enhance the proliferation and expression of TNF-β of CD8(+)HLA-DR(+)T cells from SAA patients. Such an effect is inhibited by FK506. And FK506 and FK506 plus CsA have similar effects.

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