γδT淋巴细胞及其亚型在毒性弥漫性甲状腺肿中的分布研究

Distribution of γδT lymphocytes and their subtypes in toxic diffuse goiter

目的研究γδT淋巴细胞及其亚型在毒性弥漫性甲状腺肿(GD)中的分布并探讨γδT淋巴细胞在GD免疫学发病机制中的作用。方法选取2022年6-12月上海市嘉定区中心医院内分泌门诊确诊的GD患者59例作为GD组,另选择同期65例健康志愿者作为对照组。检测两组相关甲状腺指标[包括游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)、甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TG-Ab)、抗促甲状腺激素受体抗体(TRAb)],采用流式细胞术检测两组外周血中γδT淋巴细胞及其亚型的比例,分析γδT淋巴细胞表面活化分子CD69、HLA-DR及协同刺激分子CD40配体(CD40L)与诱导性共刺激分子(ICOS)的表达水平。结果GD组TSH水平低于对照组,FT3、FT4、TPOAb、TG-Ab、TRAb水平均高于对照组,差异均有统计学意义(P<0.05)。两组γδT淋巴细胞比例比较,差异无统计学意义(P>0.05);GD组Vδ1γδT淋巴细胞比例高于对照组,Vδ2γδT淋巴细胞比例低于对照组,差异均有统计学意义(P<0.05)。GD组γδT淋巴细胞表面活化分子CD69、HLA-DR表达水平及协同刺激分子CD40L、ICOS的表达水平均明显高于对照组,差异均有统计学意义(P<0.05)。结论GD患者外周血γδT淋巴细胞亚型改变表现为Vδ1γδT淋巴细胞比例上调与Vδ2γδT淋巴细胞比例下调,γδT淋巴细胞功能活化并表达协同刺激分子CD40L、ICOS可能是促进GD产生自身抗体及自身体液免疫应答的重要病理机制。

Objective To investigate the distribution of γδT lymphocytes and their subtypes in toxic diffuse goiter(GD),and to explore the role of γδT lymphocytes in the immunological pathogenesis of GD.Methods A total of 59 GD patients diagnosed in the endocrinology clinic of the Central Hospital of Shanghai Jiading District from June 2022 to December 2022 were selected as the GD group,and 65 healthy volunteers in the same period were selected as the control group.Two groups of relevant thyroid indicators[including free triiodothyronine(FT3),free thyroxine(FT4),thyrotropin(TSH),thyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TG-Ab),anti-thyrotropin receptor antibody(TRAb)] were detected.Flow cytometry was used to detect the proportion of γδT lymphocytes and their subtypes in peripheral blood of the two groups,and the expression levels of activating molecules CD69,HLA-DR,co-stimulatory molecules CD40 ligand(CD40L) and inducible co-stimulator molecule(ICOS) on the surface of γδT lymphocytes were analyzed.Results The level of TSH in the GD group was lower than that in the control group,and the levels of FT3,FT4,TPOAb,TG-Ab and TRAb were higher than those in the control group,and the differences were statistically significant(P<0.05).There was no significant difference in the proportion of γδT lymphocytes between the two groups(P>0.05).The GD group had a significantly higher proportion of Vδ1γδT lymphocytes and a significantly lower proportion of Vδ2γδT lymphocytes than the control group(P<0.05).The expression levels of activating molecules CD69 and HLA-DR and costimulatory molecules CD40L and ICOS on γδT lymphocytes in GD group were significantly higher than those in control group(P<0.05).Conclusion The proportion of Vδ1γδT cells is up-regulated and Vδ2γδT cells is down-regulated in GD patients.The activation of γδT cells and the expression of costimulatory molecules CD40L and ICOS may be an important pathological mechanism to promote the production of autoantibodies and autoimmune humoral immune response in GD.