| Part Ⅰ Characteristics and Clinical Significance of Autoreactive CD8+ T Cells in Autoimmune Thyroid DiseaseObjective The aim of this study was to recognize thyroid antigens specific CD8+T cell epitopes and explore the relationship between these epitopes and thyroid autoantibodies,duration and classification of AITD.Methods A total of 534 Chinese patients with AITD(290 HT and 244 GD)and 177 healthy controls were recruited,of which 38 HLA-A*0201 AITD patients(13 GD and 25 HT)and 16 HLA-A*0201 healthy controls were chosen by HLA-A genotyping.HLA class Ⅰ peptide affinity algorithms were applied to predict candidate thyroid autoantigen peptides that blind to HLA-A2.CD8+T cell interferon enzyme-linked immunospot(ELISopt)assay was used to detect Tg-,TPO-and TSHR-specific CD8+T cells.Results TG-6,TG-7,TG-10,TG-11 and TPO-6 were immunodominant in GD patients compared with HT patients(TG-6:38.5%vs.8%,P=0.034;TG-7,TG-10,TG-11 and TPO-6:23.1%vs.0%,P=0.034).The immunodominance of TG-6 in GD patients was more evident than healthy controls.(TG-6:35.8%vs.0%,P=0.01 1),but there was no statistically significant difference between HT patients and healthy controls.Subgroup analyses revealed the T cell responsiveness to TG-6 was stronger in TgAb-negative HT patients(0%vs.40%,P=0.033).However,there was no correlation seen for TPOAb TRAb,medication and duration in both HT and GD patients.Conclusion It was reported for the first time that TG-6 is a Tg-specific HLA-restricted CD8+ T cell epitope of GD patients.Screening of thyroid-specific T cell epitopes and the characterization of autoreactive CD8+ T-cells will contribute to the prediction,diagnosis and typing of AITD,which may become a new target for the potential treatment of diseases.Part Ⅱ Characteristics and Clinical Significance of Follicular Helper T cells in Autoimmune Thyroid DiseasesObjective The aim of our study was to observe the frequency of follicular helper T cells(Tfh)and the expression its functional molecules(ICOS and PD-1)in patients with autoimmune thyroid disease and explore the role of Tfh in the pathogenesis of AITDMethods A total of 104 patients with autoimmune thyroid diseases,20 patients with non-autoimmune thyroid disease and 43 healthy controls were recruited.Flow cytometry was used to detect the frequency of Tfh cells and expression of ICOS and PD-1 in the peripheral blood and FNA samples.Results Compared with nAITD patients,the expression of ICOS of thyroid Tfh cells in FNA samples of HT patients was significantly increased(11.15±13.56%vs 22.24±16.16%,P=0.008).A total of 14 AITD patients had both peripheral blood and FNA samples,of which Tfh cells frequency and ICOS and PD-1 expression in thyroid gland were significantly higher than those in peripheral blood(32.86±17.00%vs 16.07±4.02%,P=0.003;12.13±7.86%vs 2.33±0.88%,P=0.000;24.79±14.67%vs 7.23±2.05%,P=0.001).The expression of ICOS and PD-1 of Tfh cells in thyroid gland of AITD patients was significantly correlated with the frequency of Tfh cells(r=0.7734,P<0.0001;r=0.9486,P<0.0001),There was a significantly positive correlation between serum TgAb level and Tfh frequency(r=0.3276,P=0.0068),and also the expression of ICOS and PD-1(r-0.3989,P=0.001 1;r=0.4035,P=0.0009).The expression of ICOS and PD-1 of cTfh in AITD patients was positively correlated with the frequency of cTfh cells(r=0.3825,P=0.0178;r=0.9035,P<0.0001).TgAb(r=0.7161,P=0.03)and TPOAb(r=0.6886,P=0.0403)levels were positively correlated with ICOS expression of cTfh in HT patients.Conclusion In this study,the frequency and expression characteristics of thyroid Tfh in FNA specimens were detected for the first time.In AITD patients,the expression of Tfh in thyroid gland and surface markers ICOS and PD-1 was significantly higher than that in peripheral blood,and the level of thyroid autoantibodies was significantly associated with Tfh frequency.Tfh cells may participate in the pathogenesis of AITD cellular immunity and regulates the formation of thyroid autoantibodies,which may become a new target for disease diagnosis and treatment. |
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