title: [Inhibitory effects of tacrolimus on effector T cells from patients with severe aplastic anemia].
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.
authors.affiliation: Department of Hematology, General Hospital, Tianjin Medical University, Tianjin, China.
authors.forename: Qi-e
authors.initials: QE
authors.lastname: Dong
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Liu
authors.forename: Er-bao
authors.initials: EB
authors.lastname: Ruan
authors.forename: Xiao-ming
authors.initials: XM
authors.lastname: Wang
authors.forename: Guo-jin
authors.initials: GJ
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Qu
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Yu-hong
authors.initials: YH
authors.lastname: Wu
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.forename: Li-min
authors.initials: LM
authors.lastname: Xing
authors.forename: Jing
authors.initials: J
authors.lastname: Guan
authors.forename: Li-juan
authors.initials: LJ
authors.lastname: Li
authors.forename: Hua-quan
authors.initials: HQ
authors.lastname: Wang
authors.forename: Zong-hong
authors.initials: ZH
authors.lastname: Shao
mesh_terms: D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000276:immunology / Q000473:pathology*; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D006684:HLA-DR Antigens; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008233:Lymphotoxin-alpha / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D006684:HLA-DR Antigens; D007376:Interleukin-2; D008233:Lymphotoxin-alpha; D016572:Cyclosporine; D016559:Tacrolimus