Changes of CD4 +CD25highFoxp3 +regulatory T cells and their significance in childhood B-cell acute lymphocytic leukemia / 中华微生物学和免疫学杂志

ABSTRACT

Objective To investigate the changes of CD4 +CD25highFoxp3 +regulatory T (Treg) cells and their significance in immune escape of childhood B-cell acute lymphocytic leukemia ( B-ALL ) . Methods Forty-two children with B-ALL and twenty-eight age-matched healthy children were enrolled in this study.Flow cytometry analysis was performed to evaluate the proportion of CD 4 +CD25high Foxp3 +Treg cells as well as CD4 +CD25high ICOS+Foxp3 +and CD4 +CD25high ICOS-Foxp3 +subsets in peripheral blood samples.The expression of associated molecules including IL-10, TGF-β, IL-35, TGF-βRII, ICOS and CD28 at protein level were also measured by flow cytometry analysis .The transcription level of Smad3/4, TIEG1 and Itch by CD4 +T cells were determined by quantitative real-time PCR.The concentration of TGF-βin plasma was detected by enzyme-linked immunosorbent assay.Results (1)The proportion of CD4 +CD25highFoxp3 +Treg cells in children with B-ALL were significantly higher than those of health subjects (P0.05).(3)The concentra-tion of TGF-βin plasma from children with B-ALL were higher than those from control group [ ( 25 .83 ± 12.65) ng/ml vs (8.59 ±5.73) ng/ml, P<0.05].The expression of TGF-βRII and its associated mole-cules (Smad3/4, TIEG1 and Itch) by CD4 +T cells were significantly up-regulated.Moreover, an increased expression of ICOS and CD28 by CD4 +CD25highFoxp3 +Treg cells were also observed in children with B-ALL (P<0.05).Conclusion The hyper-activity of TGF-β, ICOS and CD28 signaling might be closely associ-ated with the increased proportion of CD4 +CD25high Foxp3 +Treg cells and the imbalance of its subsets in children with B-ALL.