目的: 探讨复发性自然流产(recurrent spontaneous abortion,RSA)患者T细胞中T细胞免疫球蛋白和免疫受体酪氨酸抑制基序(T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain,TIGIT)的表达情况,为其可能作为治疗靶点提供理论依据。方法: 采集21例正常早孕者及23例RSA患者的抗凝外周血,分别检测其CD3+ T细胞表面分子TIGIT的百分比及细胞因子IL-10和IFN-γ的表达情况。结果: RSA组患者TIGIT+细胞所占CD3+ T细胞的百分比为(41.52±7.17)%,高于早孕组中的该百分比[(36.09±4.03)%],差异有统计学意义(P<0.05);RSA组TIGIT+ CD3+ T细胞中IL-10阳性细胞所占百分比分别为(11.68±5.90)%,低于早孕组TIGIT+ CD3+ T细胞中IL-10阳性细胞所占百分比[(16.33±6.65)%],差异有统计学意义(P<0.05);而CD3+ T细胞中IFN-γ的表达在2组间差异无统计学意义。结论: 负性共刺激分子TIGIT在RSA患者中异常表达,可能参与了母胎免疫的调控,与RSA的发生相关。
Objective: To investigate the expression of TIGIT (T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain) on peripheral T cells in patients with recurrent spontaneous abortion(RSA). Methods: Proportion of TIGIT+ T cells and the expression of IFN-γ and IL-10 of TIGIT+ T cells were detected in 21 normal pregnant women and 23 RSA patients. Results: Compared with normal pregnant women, the proportion of TIGIT+ T cells were detected in RSA patients was significantly higher [(41.52±7.17)% vs (36.09±4.03)%)] (P<0.05), and the IL-10 expression of TIGIT+ T cells in RSA group were lower than normal pregnant group [(11.68±5.90)% vs (16.33±6.65)% ](P<0.05). The expression of IFN-γ in the two groups had no significant difference. Conclusions: The abnormal expression of TIGIT may be involved in the regulation of maternal-fetal immune tolerance and is related with the occurrence of RSA.
[1] Abbas AR, Baldwin D, Ma Y, et al.Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data[J]. Genes Immun,2005,6(4):319-331.
[2] Yu X, Harden K, Gonzalez LC, et al.The surface protein TIGIT suppresses T cell activation by promoting the gene-ration of mature immunoregulatory dendritic cells[J]. Nat Immunol,2009,10(1):48-57.
[3] Kourepini E, Paschalidis N, Simoes DC, et al.TIGIT Enhances Antigen-Specific Th2 Recall Responses and Allergic Disease[J]. J Immunol,2016,196(9):3570-3580.
[4] Joller N, Lozano E, Burkett PR, et al.Treg cells expres-sing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses[J]. Immunity,2014,40(4):569-581.
[5] Anderson AC, Joller N, Kuchroo VK.Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation[J]. Immunity,2016,44(5):989-1004.
[6] Johnston RJ, Comps-Agrar L, Hackney J, et al.The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function[J]. Cancer Cell,2014,26(6):923-937.
[7] Wang X, Ma Z, Hong Y, et al.The skewed TCR-BV repertoire displayed at the maternal-fetal interface of women with unexplained pregnancy loss[J]. Am J Reprod Immunol,2005,54(2):84-95.
[8] Wang SC, Li YH, Piao HL, et al.PD-1 and Tim-3 pathways are associated with regulatory CD8+ T-cell function in decidua and maintenance of normal pregnancy[J]. Cell Death Dis,2015,6:e1738.
[9] 林其德. 原因不明复发性流产的基础与临床研究进展[J]. 中华妇产科杂志,2003,38(8):481-483.
[10] Mucida D, Park Y, Kim G, et al. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acidScience,2007,317(5835):256-260.
[11] Wu L, Luo LH, Zhang YX, et al.Alteration of Th17 and Treg cells in patients with unexplained recurrent spontaneous abortion before and after lymphocyte immunization therapy[J]. Reprod Biol Endocrinol,2014,12:74.
[12] 张建平. NK细胞与复发性自然流产母胎免疫紊乱[J]. 中山大学学报(医学科学版),2010,31(4):451-456,481.
[13] Mahnke K, Enk AH.TIGIT-CD155 Interactions in Melanoma: A Novel Co-Inhibitory Pathway with Potential for Clinical Intervention[J]. J Invest Dermatol,2016,136(1):9-11.
[14] Pauken KE, Wherry EJ.TIGIT and CD226: tipping the balance between costimulatory and coinhibitory molecules to augment the cancer immunotherapy toolkit[J]. Cancer Cell,2014,26(6):785-787.
[15] Lozano E, Dominguez-Villar M, Kuchroo V, et al.The TIGIT/CD226 axis regulates human T cell function[J]. J Immunol,2012,188(8):3869-3875.
