Expressions of Tim-3 and PD-1 on T cells in patients with recurrent spontaneous abortion

doi:10.3969/j.issn.1673-8640.2016.06.008

Abstract

Abstract:

Objective To investigate the expressions of T cell immunoglobin mucin-3 （Tim-3） and programmed death-1 （PD-1） on T cells in patients with recurrent spontaneous abortion（RSA）,and provide a reference for target treatment. Method The expressions of Tim-3 and PD-1 on T cells were determined by flow cytometry in 22 healthy pregnant women （control group） and 21 patients with RSA. Result The proportion of Tim-3⁺ T cells in RSA group （1.01%±0.64%） was lower than that in control group （1.85%±0.96%）（P<0.01）,and the proportion of PD-1⁺ T cells in RSA group（40.76%±13.76%） was lower than that in control group （54.32%±26.65%）（P<0.05）. The proportion of Tim-3⁺ PD-1⁺ T cells in RSA group（0.59%±0.27%） was lower than that in control group（1.37%±0.85%）（P<0.001）,while the proportions of Tim-3^-PD-1⁺ and Tim-3⁺ PD-1^-T cells（40.17%±13.68% and 0.43%±0.41%） had no statistical significance with those in control group（52.95%±26.28% and 0.48%±0.31%）（P>0.05）. ConclusionsThe expressions of Tim-3⁺CD3⁺,PD-1⁺CD3⁺ and Tim-3⁺ PD-1⁺ T cells are correlated with RSA. They can be potential targets for RSA treatment.

Key words: T cell immunoglobin mucin-3, Programmed death-1, Recurrent spontaneous abortion

CLC Number:

R446.1

DUAN Zhongliang, SHI Youhao, LI Mingqing, LI Cui. Expressions of Tim-3 and PD-1 on T cells in patients with recurrent spontaneous abortion[J]. Laboratory Medicine, 2016, 31(6): 474-478.

Figures/Tables 2

References 25

[1]	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.
[2]	YUAN MM,DU MR,WANG MY,et al.Combination of CD4(+)CD25(+)CD127(-) regulatory T cells with MLC-BE and BE-Ab2:an efficient evaluation of the therapy of paternal lymphocyte induced immunization in unexplained recurrent spontaneous abortion patients[J]. Int J Clin Exp Pathol,2015,8(4):4022-4032.
[3]	ISHIDA Y,AGATA Y,SHIBAHARA K,et al.Induced expression of PD-1,a novel member of the immunoglobulin gene superfamily,upon programmed cell death[J]. EMBO J,1992,11(11):3887-3895.
[4]	LUAN Y,CHAI D,PENG J,et al.A fully human monoclonal antibody targeting PD-L1 with potent anti-tumor activity[J]. Int Immunopharmacol,2016,31:248-256.
[5]	HAN S,FENG S,XU L,et al.Tim-3 on peripheral CD4+ and CD8+ T cells is involved in the development of glioma[J]. DNA Cell Biol,2014,33(4):245-250.
[6]	WANG M,JI B,WANG J,et al.Tim-3 polymorphism downregulates gene expression and is involved in the susceptibility to ankylosing spondylitis[J]. DNA Cell Biol,2014,33(10):723-728.
[7]	LUO Q,HUANG Z,YE J,et al.PD-L1-expressing neutrophils as a novel indicator to assess disease activity and severity of systemic lupus erythematosus[J]. Arthritis Res Ther,2016,18:47.
[8]	YANG M,YU Q,LIU J,et al.T-cell immunoglobulin mucin-3 expression in bladder urothelial carcinoma:clinicopathologic correlations and association with survival[J]. J Surg Oncol,2015,112(4):430-435.
[9]	SADA-OVALLE I,OCAA-GUZMAN R,PEREZ-PATRIGEON S,et al.Tim-3 blocking rescue macrophage and T cell function against Mycobacterium tuberculosis infection in HIV+ patients[J]. J Int AIDS Soc,2015,18:20078.
[10]	GAO DN,YANG ZX,QI QH.Roles of PD-1,Tim-3 and CTLA-4 in immunoregulation in regulatory T cells among patients with sepsis[J]. Int J Clin Exp Med,2015,8(10):18998-19005.
[11]	贾秋桦,于斐. Tim-3在不明原因复发性流产患者绒毛和蜕膜组织中的表达[J]. 山东大学学报(医学版),2014,59(10):81-85.
[12]	LI J,LI FF,ZUO W,et al.Up-regulated expression of Tim-3/Gal-9 at maternal-fetal interface in pregnant woman with recurrent spontaneous abortion[J]. J Huazhong Univ Sci Technolog Med Sci,2014,34(4):586-590.
[13]	WANG S,ZHU X,XU Y,et al.Programmed cell death-1 (PD-1) and T-cell immunoglobulin mucin-3 (Tim-3) regulate CD4+ T cells to induce type 2 helper T cell (Th2) bias at the maternal-fetal interface[J]. Hum Reprod,2016,31(4):700-711.
[14]	KHESHTCHIN N,GHARAGOZLOO M,ANDALIB A,et al.The expression of Th1- and Th2-related chemokine receptors in women with recurrent miscarriage:the impact of lymphocyte immunotherapy[J]. Am J Reprod Immunol,2010,64(2):104-112.
[15]	MUCIDA D,PARK Y,KIM G,et al.Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid[J]. Science,2007,317(5835):256-260.
[16]	MARKWICK LJ,RIVA A,RYAN JM,et al.Blockade of PD1 and TIM3 restores innate and adaptive immunity in patients with acute alcoholic hepatitis[J]. Gastroenterology,2015,148(3):590-602.
[17]	SEKI M,OOMIZU S,SAKATA KM,et al.Galectin-9 suppresses the generation of Th17,promotes the induction of regulatory T cells,and regulates experimental autoimmune arthritis[J]. Clin Immunol,2008,127(1):78-88.
[18]	LATCHMAN Y,WOOD CR,CHERNOVA T,et al.PD-L2 is a second ligand for PD-1 and inhibits T cell activation[J]. Nat Immunol,2001,2(3):261-268.
[19]	KEIR ME,BUTTE MJ,FREEMAN GJ,et al.PD-1 and its ligands in tolerance and immunity[J]. Annu Rev Immunol,2008,26:677-704.
[20]	KOBAYASHI M,KAWANO S,HATACHI S,et al.Enhanced expression of programmed death-1 (PD-1)/PD-L1 in salivary glands of patients with Sjgren's syndrome[J]. J Rheumatol,2005,32(11):2156-2163.
[21]	GUPTA S,THORNLEY TB,GAO W,et al.Allograft rejection is restrained by short-lived TIM-3+PD-1+Foxp3+ Tregs[J]. J Clin Invest,2012,122(7):2395-2404.
[22]	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.
[23]	RENAUD SJ,COTECHINI T,QUIRT JS,et al.Spontaneous pregnancy loss mediated by abnormal maternal inflammation in rats is linked to deficient uteroplacental perfusion[J]. J Immunol,2011,186(3):1799-1808.
[24]	MATTHIESEN L,KALKUNTE S,SHARMA S.Multiple pregnancy failures:an immunological paradigm[J]. Am J Reprod Immunol,2012,67(4):334-340.
[25]	TAYLOR DD,GERCEL-TATLOR C.Alterations in T-cell signal transduction molecules associated with recurrent spontaneous pregnancy loss[J]. J Reprod Immunol,2004,63(2):137-154.