HLA-E的表达对RSA及PIH患者外周血γδT细胞细胞毒效应的影响

探索HLA-E分子的表达对习惯性流产(recurrent spontaneous abortion,RSA)及妊高症(pregnancy-induced hypertension,PIH)患者外周血γδT细胞细胞毒效应的影响。通过固相抗体法体外分离并扩增外周γδT血细胞作为效应细胞,以HLA-E转染的LcL721.221细胞(.221E)及滋养层细胞JAR作为靶细胞,采用4 h乳酸脱氢酶(LDH)释放试验观察NK细胞对靶细胞的细胞毒效应。结果显示,来自RSA、PIH及正常对照组的γδ细胞均不能有效杀伤HLA-E转染的.221E细胞及JAR细胞,但未经HLA-E转染的LcL721.221细胞则被溶解;抗HLA-E单抗3D12及抗CD94单抗HP-3B1的阻断可以分别部分恢复效应细胞对靶细胞LcL721.221E的杀伤,但对JAR细胞没有影响;与正常对照组相比,RSA及PIH患者外周血γδT细胞对.221、.221E及JAR细胞的细胞毒活性没有显著性差异(P>0.05)。这说明HLA-E分子的体外表达可以保护靶细胞防止γδT细胞的杀伤,该保护机制主要是通过γδT细胞受体CD94/NKG2对靶细胞表面HLA-E分子的识别来实现的;滋养层细胞对γδT细胞杀伤的抵抗可能存在MHC I类非依赖的机制。

The Influences of HLA-E Expression on Cytotoxicities of γδ T Cells from Patients with RSA and PIH

To explore the influences of HLA-E molecules in vitro on the cytotoxicity of y?T cells from patients with recurrent spontaneous abortion (RSA )and pregnancy-induced hypertension (PIH ) , solid-phase antibody method was used to isolate and proliferate the γδ T cells of RSA and PIH patients. Lactate dehydrogenase ( LDH ) release assay was employed to detect the cytotoxicity of yS T cells proliferated in vitro against HLA-E transfectants LcL721.221 cells (.221E ) and trophoblast cell line JAR. Results showed that: a failure to killing was detected for j8 T cells from RSA, PIH and controls against.221E and JAR, but the killing was detected for these γδ T cells against LcL721.221 cells. The blockings of McAb 3D12 (anti-HLA-E )and HP-3B1 (anti-CD94 )was able to resolve the killings of γδ T cells against the .221E respectively in part, but no resolved killings against JAR cells could be found for these blockings. No significant difference could be found for cytotoxicities of yS T cell against targets between RSA or PIH and controls. The expression of HLA-E on cell surface in vitro can protect targets against the killing of yS T cells, and the molecular mechanism mainly involves in the recognition of CD94/NKG2 γδ T receptor to HLA-E molecules expressed on targets; The resistance of trophoblast to γδ T cells maybe involved in the independent mechanism.