[Expression of transcription factors T-bet/GATA-3 mRNA and its effect on Tc1/Tc2 balance in asthmatic children].

ABSTRACT

OBJECTIVE: In contrast to CD(4)(+) helper T-lymphocytes (T(H)), little is known about the transcriptional regulation of CD(8)(+) cytotoxic T-lymphocytes (Tc) and its role in the pathogenesis of asthma is unclear. This study was conducted to investigate the effect of T-bet and GATA-3 mRNA expression on profiles of type 1 and type 2 cytotoxic T lymphocytes in asthmatic children. METHOD: Totally 38 asthmatic children, including acute attack group composed of 20 cases (age 3 - 13 years, mean 6.2 +/- 2.9), remission group with 18 cases (age 3 - 12 years, mean 6.1 +/- 2.5) and 20 healthy control children (age 3 - 12, 6.9 +/- 2.7) were recruited in this study from Sep. 2005 to Mar. 2006. The mRNA expression of T-bet and GATA-3 in the peripheral blood mononuclear cells were detected by using semi-quantitative PCR and Tc1, Tc2 cell numbers by flow cytometry analysis system. RESULT: T-bet mRNA in asthmatic children was lower than that in control group and lower in attack stage than in remission stage (0.14 +/- 0.04, 0.21 +/- 0.03, 0.28 +/- 0.03, P < 0.05). In contrast, GATA-3 mRNA was higher in asthmatic children than in control group and higher in attack stage than in remission stage (0.49 +/- 0.09, 0.44 +/- 0.08, 0.37 +/- 0.04, P < 0.05). It was shown that Tc1 percentage was lower in asthmatic children than those of control group and lower in attack stage than those of remission stage (6.6 +/- 2.4, 14.2 +/- 4.3, 31.2 +/- 3.8, P < 0.05). Tc2 percentage in asthmatic children was higher than that of control group and higher in attack stage than that of remission stage (10.0 +/- 4.2, 5.4 +/- 2.2, 3.5 +/- 1.1, P < 0.05). Spearman correlation analysis revealed that T-bet mRNA was positively correlated with Tc1 percentage (r = 0.704) and negatively correlated with Tc2 percentage (r = -0.629). GATA3 mRNA was negatively correlated with Tc1 percentage (r = -0.612) and positively correlated with Tc2 percentage (r = 0.673). The T-bet/GATA-3 mRNA ratio was positively correlated with Tc1 percentage (r = 0.731) and Tc1/Tc2 (r = 0.773), while negatively correlated with Tc2 percentage (r = -0.642). CONCLUSION: The imbalance of T-bet/GATA-3 mRNA expression is closely correlated with skewed Tc2 dominance in asthmatic children.