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Allergy, Asthma & Clinical Immunology
Published in: Allergy, Asthma & Clinical Immunology 1/2017

Open Access 01-12-2017 | Research

Elevated expression of TIGIT on CD3+CD4+ T cells correlates with disease activity in systemic lupus erythematosus

Authors: Qing Luo, Jianqing Ye, Lulu Zeng, Xue Li, Le Fang, Beihua Ju, Zikun Huang, Junming Li

Published in: Allergy, Asthma & Clinical Immunology | Issue 1/2017

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Abstract

Objectives

It is well-known that lymphocytes play an important role in systemic lupus erythematosus (SLE). T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory domains (TIGIT) is one of immunosuppressive costimulatory molecules that mediates an inhibitory effect. However, its roles in SLE are poorly understood. This study was designed to investigate the correlation between the frequencies of TIGIT-expressing CD3+CD4+ T lymphocytes and SLE.

Methods

Patients with SLE were recruited from the First Affiliated Hospital of Nanchang University. Medical history, clinical manifestations, physical examination and laboratory measurements were recorded. The expression of TIGIT on CD3+ T lymphocytes, B lymphocytes, monocytes, neutrophils, CD3+CD4+ T lymphocytes and CD3+CD8+ T lymphocytes were determined by flow cytometry. The frequencies of TIGIT-expressing CD3+CD4+ T lymphocytes in patients with SLE were further analyzed for correlations with markers of autoimmune response, inflammation, urine proteins and disease activity in SLE.

Results

The frequency of TIGIT-expressing CD3+CD4+ T lymphocytes was significantly elevated in SLE patients compared with healthy controls (P < 0.0001). The frequency of TIGIT-expressing CD3+CD4+ T lymphocytes in patients with SLE was increased significantly in subjects with high anti-dsDNA titer (P = 0.026), high anti-Sm titer (P = 0.026), and high levels of urine microalbumin (P = 0.046). Furthermore, The frequency of TIGIT-expressing CD3+CD4+ T lymphocytes was found to be positively correlated with the Disease Activity Index (SLEDAI) score in SLE (r2 = 0.082; P = 0.044).

Conclusion

In SLE, the frequency of TIGIT-expressing CD3+CD4+ T lymphocytes was elevated and associated with the disease activity.
Literature
1.
2.
Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of immunosuppressants in systemic lupus erythematosus: a systematic review. Ann Rheum Dis. 2010;69:20–8.CrossRefPubMed
3.
4.
5.
Voll RE, Roth EA, Girkontaite I, Fehr H, Herrmann M, Lorenz HM, et al. Histone-specific Th0 and Th1 clones derived from systemic lupus erythematosus patients induce double-stranded DNA antibody production. Arthritis Rheum. 1997;40:2162–71.CrossRefPubMed
6.
Lawson BR, Koundouris SI, Barnhouse M, Dummer W, Baccala R, Kono DH, et al. The role of αβ+ T cells and homeostatic T cell proliferation in Y-chromosome-associated murine lupus. J Immunol. 2001;167:2354–60.CrossRefPubMed
7.
Wong CK, Lit LC, Tam LS, Li EK, Lam CW. Aberrant production of soluble costimulatory molecules CTLA-4, CD28, CD80 and CD86 in patients with systemic lupus erythematosus. Rheumatology. 2005;44:989–94.CrossRefPubMed
8.
Stanietsky N, Simic H, Arapovic J, Toporik A, Levy O, Novik A, et al. The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proc Natl Acad Sci USA. 2009;106:17858–63.CrossRefPubMedPubMedCentral
9.
Joller N, Hafler JP, Brynedal B, Kassam N, Spoerl S, Levin SD, et al. Cutting edge: TIGIT has T cell-intrinsic inhibitory functions. J Immunol. 2011;186:1338–42.CrossRefPubMedPubMedCentral
10.
Stanietsky N, Rovis TL, Glasner A, Seidel E, Tsukerman P, Yamin R, et al. Mouse TIGIT inhibits NK-cell cytotoxicity upon interaction with PVR. Eur J Immunol. 2013;43:2138–50.CrossRefPubMedPubMedCentral
11.
Li M, Xia P, Du Y, Liu S, Huang G, Chen J, et al. T-cell immunoglobulin and ITIM domain (TIGIT) receptor/poliovirus receptor (PVR) ligand engagement suppresses interferon-gamma production of natural killer cells via β-arrestin 2-mediated negative signaling. J Biol Chem. 2014;289:17647–57.CrossRefPubMedPubMedCentral
12.
Joller N, Lozano E, Burkett PR, Patel B, Xiao S, Zhu C, et al. Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses. Immunity. 2014;40:569–81.CrossRefPubMedPubMedCentral
13.
Wang F, Hou H, Wu S, Tang Q, Liu W, Huang M, et al. TIGIT expression levels on human NK cells correlate with functional heterogeneity among healthy individuals. Eur J Immunol. 2015;45:2886–97.CrossRefPubMed
14.
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.CrossRefPubMed
15.
Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum. 1992;35:630–40.CrossRefPubMed
16.
Rheumatology branch of Chinese medical association. Guide for diagnosis and treatment of systemic lupus erythematosus. Chin J Rheumatol. 2010;14:342–6.
17.
Bertsias GK, Nakou M, Choulaki C, Raptopoulou A, Papadimitraki E, Goulielmos G, et al. Genetic, immunologic, and immunohistochemical analysis of the programmed death 1/programmed death ligand 1 pathway in human systemic lupus erythematosus. Arthritis Rheum. 2009;60:207–18.CrossRefPubMed
18.
Liu MF, Weng CT, Weng MY. Variable increased expression of program death-1 and program death-1 ligands on peripheral mononuclear cells is not impaired in patients with systemic lupus erythematosus. J Biomed Biotechnol. 2009;2009:406136.PubMedPubMedCentral
19.
Luo Q, Huang Z, Ye J, Deng Y, Fang L, Li X, et al. PD-L1-expressing neutrophils as a novel indicator to assess disease activity and severity of systemic lupus erythematosus. Arthritis Res Ther. 2016. doi:10.​1186/​s13075-016-0942-0.
20.
Isenberg DA, Manson JJ, Ehrenstein MR, Rahman A. Fifty years of anti-dsDNA antibodies: are we approaching journey’s end? Rheumatology. 2007;46:1052–6.CrossRefPubMed
21.
22.
23.
Petri M, Kasitanon N, Lee SS, Link K, Magder L, Bae SC, et al. Systemic lupus international collaborating clinics renal activity/response exercise: development of a renal activity score and renal response index. Arthritis Rheum. 2008;58:1784–8.CrossRefPubMed
24.
Ouyang H, Shi Y, Liu Z, Feng S, Li L, Su N, et al. Increased interleukin-9 and CD4+IL-9+ T cells in patients with systemic lupus erythematosus. Mol Med Rep. 2013;7:1031–7.PubMed
25.
Akhter E, Burlingame RW, Seaman AL, Magder L, Petri M. Anti-C1q antibodies have higher correlation with flares of lupus nephritis than other serum markers. Lupus. 2011;20:1267–74.CrossRefPubMed
26.
Ma H, Wan S, Xia C. New insights into the immunopathogenesis of systemic lupus erythematosus: the role of T follicular helper cells. Chin Med J. 2014;127:3496–502.PubMed
27.
Song LJ, Wang X, Wang XP, Li D, Ding F, Liu HX, et al. Increased Tim-3 expression on peripheral T lymphocyte subsets and association with higher disease activity in systemic lupus erythematosus. Diagn Pathol. 2015;10:71.CrossRefPubMedPubMedCentral
28.
Liu MF, Liu HS, Wang CR, Lei HY. Expression of CTLA-4 molecule in peripheral blood T lymphocytes from patients with systemic lupus erythematosus. J Clin Immunol. 1998;18:392–8.CrossRefPubMed
29.
30.
Okamura T, Sumitomo S, Morita K, Iwasaki Y, Inoue M, Nakachi S, et al. TGF-β3-expressing CD4+CD25−LAG3+ regulatory T cells control humoral immune responses. Nat Commun. 2015;6:6329.CrossRefPubMedPubMedCentral
31.
32.
Dorner T, Jacobi AM, Lee J, Lipsky PE. Abnormalities of B cell subsets in patients with systemic lupus erythematosus. J Immunol Methods. 2011;363:187–97.CrossRefPubMed
33.
Maeda N, Sekigawa I, Iida N, Matsumoto M, Hashimoto H, Hirose S. Relationship between CD4+/CD8+ T cell ratio and T cell activation in systemic lupus erythematosus. Scand J Rheumatol. 1999;28:166–70.CrossRefPubMed
34.
Shah D, Kiran R, Wanchu A, Bhatnagar A. Relationship between T lymphocyte subsets and cortisol in systemic lupus erythematosus. Kathmandu Univ Med J. 2009;7:213–9.
35.
36.
Chavez-Rueda K, Legorreta-Haquet MV, Cervera-Castillo H, Sánchez L, Jara LJ, Zenteno E, et al. Prolactin effect on CD69 and CD154 expression by CD4+ cells from systemic lupus erythematosus patients. Clin Exp Rheumatol. 2005;23:769–77.PubMed
37.
Crispin JC, Martínez A, de Pablo P, Velasquillo C, Alcocer-Varela J. Participation of the CD69 antigen in T-cell activation process of patients with systemic lupus erythematosus. Scand J Immunol. 1998;48:196–200.CrossRefPubMed
38.
Boles KS, Vermi W, Facchetti F, Fuchs A, Wilson TJ, Diacovo TG, et al. A novel molecular interaction for the adhesion of follicular CD4 T cells to follicular DC. Eur J Immunol. 2009;39:695–703.CrossRefPubMedPubMedCentral
39.
Godefroy E, Zhong H, Pham P, Friedman D, Yazdanbakhsh K. TIGIT-positive circulating follicular helper T cells display robust B-cell help functions: potential role in sickle cell alloimmunization. Haematologica. 2015;100:1415–25.CrossRefPubMedPubMedCentral
40.
Ohl K, Tenbrock K. Regulatory T cells in systemic lupus erythematosus. Eur J Immunol. 2015;45:344–55.CrossRefPubMed
Metadata
Title
Elevated expression of TIGIT on CD3+CD4+ T cells correlates with disease activity in systemic lupus erythematosus
Authors
Qing Luo
Jianqing Ye
Lulu Zeng
Xue Li
Le Fang
Beihua Ju
Zikun Huang
Junming Li
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Allergy, Asthma & Clinical Immunology / Issue 1/2017
Electronic ISSN: 1710-1492
DOI
https://doi.org/10.1186/s13223-017-0188-7

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