了解慢性乙型肝炎(CHB)患者外周血CD4⁺CD25⁺Foxp3⁺调节性T细胞(Treg)水平及其在乙型肝炎病毒(HBV)感染中的作用。

采用流式细胞仪检测86例CHB患者、30名急性乙型肝炎(AHB)患者和30例健康体检者外周血CD4⁺CD25⁺Foxp3⁺Treg频率,分析HBV DNA载量与CD4⁺CD25⁺Foxp3⁺Treg频率的关系及治疗后不同疗效的CD4⁺CD25⁺Foxp3⁺Treg频率,并对轻度、中度和重度CHB患者的CD4⁺CD25⁺Foxp3⁺Treg频率进行比较。

CHB组外周血CD4⁺CD25⁺Foxp3⁺Treg占CD4⁺T细胞的百分比为2.56%±1.12%,明显高于AHB组(1.39%±0.68%)和正常对照组(1.45%±0.76%)(P<0.05),而AHB组与正常对照组之间差异无统计学意义(P>0.05)。轻度、中度和重度活动性CHB各组之间外周血CD4⁺CD25⁺Foxp3⁺Treg频率差异均无统计学意义(P>0.05)。CHB组、AHB组外周血ALT水平分别为285.6±168.3、(780.9±432.6)U/L,均明显高于正常对照组[(23.2±6.7)U/L](P<0.05),CHB组低于AHB组(P<0.05)。CHB患者外周血CD4⁺CD25⁺Foxp3⁺Treg频率与ALT水平无相关性(r=0.11,P>0.05)。CHB组、AHB组和正常对照组外周血HBV DNA分别为(5.2±1.8)log₁₀拷贝/mL、(7.2±1.8)log₁₀拷贝/mL和阴性,AHB组明显高于CHB组(P<0.05)。CHB患者外周血CD4⁺CD25⁺Foxp3⁺Treg频率与HBV DNA的对数呈正相关(r=0.30,P<0.05)。经抗病毒治疗后,疗效明显的CHB患者外周血CD4⁺CD25⁺Foxp3⁺Treg频率下降,明显低于疗效不明显组(P<0.05)。

CD4⁺CD25⁺Foxp3⁺Treg升高可能是HBV感染慢性化的重要因素之一,调节CD4⁺CD25⁺Foxp3⁺Treg的数量和功能可能为治疗CHB提供一个新途径。

To investigate the frequency of CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Treg)in peripheral blood of patients with chronic hepatitis B (CHB)and its significance in the hepatitis B virus (HBV)infection.

The frequencies of CD4⁺CD25⁺Foxp3⁺Treg in peripheral blood from 86 CHB patients,30 acute hepatitis B (AHB)patients and 30 healthy subjects were determined by flow cytometry.The correlations of HBV DNA loads with CD4⁺CD25⁺Foxp3⁺ Treg frequency and the frequency of CD4⁺CD25⁺Foxp3⁺ Treg after therapy with different therapeutic effects were analyzed respectively.CD4⁺CD25⁺Foxp3⁺ Treg frequencies among mild,moderate and severe active CHB patients were compared respectively.

The percentages of CD4⁺CD25⁺Foxp3⁺ Treg in CHB patients,AHB patients and healthy subjects were 2.56%±1.12%,1.39%±0.68% and 1.45%±0.76%, respectively.The percentage in CHB patients was higher than those in AHB patients and healthy subjects (P<0.05),and there was no statistical significance between the percentages of AHB patients and healthy subjects (P>0.05).The percentages of CD4⁺CD25⁺Foxp3⁺ Treg among mild,moderate and severe active CHB patients had no statistical significance (P>0.05).The levels of alanine aminotransferase (ALT)in CHB patients,AHB patients and healthy subjects were 285.6±168.3,(780.9±432.6) and (23.2±6.7) U/L, respectively.The levels of ALT in CHB patients and AHB patients were higher than that in healthy subjects(P<0.05).The level of ALT in CHB patients was lower than that in AHB patients(P<0.05).The frequency of CD4⁺CD25⁺Foxp3⁺ Treg was not correlated with the level of ALT (r=0.11,P>0.05).The HBV DNA loads in CHB patients,AHB patients and healthy subjects were (5.2±1.8)log₁₀copies/mL,(7.2±1.8)log₁₀copies/mL and negative respectively.The HBV DNA load in AHB patients was higher than that in CHB patients(P<0.05).There was a positive correlation between CD4⁺CD25⁺Foxp3⁺ Treg frequency and HBV DNA logarithm(r=0.30,P<0.05).CD4⁺CD25⁺Foxp3⁺ Treg frequency decreased obviously after anti-viral therapy in the patients with obvious good therapeutic effect,and it was lower than that in the patients with poor therapeutic effect (P<0.05).

The increase of CD4⁺CD25⁺Foxp3⁺ Treg in CHB patients plays an active role in chronic HBV.The regulation and control of function and amount of CD4⁺CD25⁺Foxp3⁺ Treg may provide a new therapy for CHB.