Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Immunology
Published in: BMC Immunology 1/2021

Open Access 01-12-2021 | Stable Angina Pectoris | Research article

CD100 modulates cytotoxicity of CD8+ T cells in patients with acute myocardial infarction

Authors: Yan Li, Li Qin, Qijun Bai, Jingjing Zhang, Ruixue Chen, Kunpeng Song

Published in: BMC Immunology | Issue 1/2021

Login to get access

Abstract

Background

CD100 is an immune semaphorin family member that highly expressed on T cells, which take part in the development of acute myocardial infarction (AMI). Matrix metalloproteinases (MMPs) are important mediators for membrane-bound CD100 (mCD100) shedding from T cells to generate soluble CD100 (sCD100), which has immunoregulatory effect on T cells. The aim of this study was to investigate modulatory role of CD100 on CD8+ T cell activity in AMI patients.

Methods

Peripheral sCD100 and MMP-2 level, as well as mCD100 level on T cells was assessed in patients with stable angina pectoris (SAP), unstable angina pectoris (UAP), and AMI. The regulatory function of MMP-2 on mCD100 shedding, sCD100 formation, and cytotoxicity of CD8+ T cells was analyzed in direct and indirect contact co-culture system.

Results

AMI patients had higher peripheral sCD100 and lower mCD100 expression on CD8+ T cells in comparison with SAP, UAP, and controls. CD8+ T cells in AMI patients showed elevated direct cytotoxicity, enhanced cytokine production, and increased perforin/granzyme B secretion. Recombinant sCD100 stimulation promoted cytolytic function of CD8+ T cells in controls and AMI patients. Furthermore, AMI patients also had elevated circulating MMP-2 level. Recombinant MMP-2 stimulation induced mCD100 shedding from CD8+ T cells and sCD100 generation, resulting in enhancement of CD8+ T cell cytotoxicity in AMI patients.

Conclusion

Up-regulation of MMP-2 might contribute to elevation of mCD100 shedding and sCD100 formation, leading to increased cytotoxicity CD8+ T cells in AMI patients.
Literature
1.
Bentzon JF, Otsuka F, Virmani R, Falk E. Mechanisms of plaque formation and rupture. Circ Res. 2014;114(12):1852–66.PubMedCrossRef
2.
Wang C, Hu S, Wu J, Yu H, Pan W, Qin Y, He L, Li L, Hou J, Zhang S, et al. Characteristics and significance of healed plaques in patients with acute coronary syndrome and stable angina: an in vivo OCT and IVUS study. EuroIntervention. 2019;15(9):e771–8.PubMedCrossRef
3.
4.
5.
Matusik P, Guzik B, Weber C, Guzik TJ. Do we know enough about the immune pathogenesis of acute coronary syndromes to improve clinical practice? Thromb Haemost. 2012;108(3):443–56.PubMedCrossRef
6.
Elabbassi W, Al-Nooryani A. Acute coronary syndrome. An acute inflammatory syndrome. Saudi Med J. 2006;27(12):1799–803.PubMed
7.
Flego D, Liuzzo G, Weyand CM, Crea F. Adaptive immunity Dysregulation in acute coronary syndromes: from cellular and molecular basis to clinical implications. J Am Coll Cardiol. 2016;68(19):2107–17.PubMedPubMedCentralCrossRef
8.
Yan X, Anzai A, Katsumata Y, Matsuhashi T, Ito K, Endo J, Yamamoto T, Takeshima A, Shinmura K, Shen W, et al. Temporal dynamics of cardiac immune cell accumulation following acute myocardial infarction. J Mol Cell Cardiol. 2013;62:24–35.PubMedCrossRef
9.
Gang H, Peng D, Hu Y, Tang S, Li S, Huang Q. Interleukin-9-secreting CD4(+) T cells regulates CD8(+) T cells cytotoxicity in patients with acute coronary syndromes. APMIS. 2021;129(2):91–102.PubMedCrossRef
10.
Elhabazi A, Marie-Cardine A, Chabbert-de Ponnat I, Bensussan A, Boumsell L. Structure and function of the immune semaphorin CD100/SEMA4D. Crit Rev Immunol. 2003;23(1–2):65–81.PubMedCrossRef
11.
Kuklina EM. Receptor functions of Semaphorin 4D. Biochemistry (Mosc). 2019;84(9):1021–7.CrossRef
12.
Luque MC, Gutierrez PS, Debbas V, Martins WK, Puech-Leao P, Porto G, Coelho V, Boumsell L, Kalil J, Stolf B. Phage display identification of CD100 in human atherosclerotic plaque macrophages and foam cells. PLoS One. 2013;8(9):e75772.PubMedPubMedCentralCrossRef
13.
14.
Yang S, Wang L, Pan W, Bayer W, Thoens C, Heim K, Dittmer U, Timm J, Wang Q, Yu Q, et al. MMP2/MMP9-mediated CD100 shedding is crucial for inducing intrahepatic anti-HBV CD8 T cell responses and HBV clearance. J Hepatol. 2019;71(4):685–98.PubMedCrossRef
15.
Wang HM, Zhang XH, Ye LQ, Zhang K, Yang NN, Geng S, Chen J, Zhao SX, Yang KL, Fan FF. Insufficient CD100 shedding contributes to suppression of CD8(+) T-cell activity in non-small cell lung cancer. Immunology. 2020;160(2):209–19.PubMedCrossRef
16.
Lu Q, Dong N, Wang Q, Yi W, Wang Y, Zhang S, Gu H, Zhao X, Tang X, Jin B, et al. Increased levels of plasma soluble Sema4D in patients with heart failure. PLoS One. 2013;8(5):e64265.PubMedPubMedCentralCrossRef
17.
Willner N, Goldberg Y, Schiff E, Vadasz Z. Semaphorin 4D levels in heart failure patients: a potential novel biomarker of acute heart failure? ESC Heart Fail. 2018;5(4):603–9.PubMedPubMedCentralCrossRef
18.
Xiang L, You T, Chen J, Xu W, Jiao Y. Serum soluble Semaphorin 4D is associated with left atrial diameter in patients with atrial fibrillation. Med Sci Monit. 2015;21:2912–7.PubMedPubMedCentralCrossRef
19.
Dhillon OS, Khan SQ, Narayan HK, Ng KH, Mohammed N, Quinn PA, Squire IB, Davies JE, Ng LL. Matrix metalloproteinase-2 predicts mortality in patients with acute coronary syndrome. Clin Sci (Lond). 2009;118(4):249–57.CrossRef
20.
Sun H, Zhang J, Zheng Y, Shang S. Expressions and clinical significance of factors related to acute coronary syndrome. J Biol Regul Homeost Agents. 2018;32(2):299–305.PubMed
21.
Ma F, Feng J, Zhang C, Li Y, Qi G, Li H, Wu Y, Fu Y, Zhao Y, Chen H, et al. The requirement of CD8+ T cells to initiate and augment acute cardiac inflammatory response to high blood pressure. J Immunol. 2014;192(7):3365–73.PubMedCrossRef
22.
Groschel C, Sasse A, Monecke S, Rohrborn C, Elsner L, Didie M, Reupke V, Bunt G, Lichtman AH, Toischer K, et al. CD8(+)-T cells with specificity for a model antigen in Cardiomyocytes can become activated after transverse aortic constriction but do not accelerate progression to heart failure. Front Immunol. 2018;9:2665.PubMedPubMedCentralCrossRef
23.
Zhang L, Wang Z, Wang D, Zhu J, Wang Y. CD8(+)CD28(+) T cells might mediate injury of cardiomyocytes in acute myocardial infarction. Mol Immunol. 2018;101:74–9.PubMedCrossRef
24.
Tae Yu H, Youn JC, Lee J, Park S, Chi HS, Lee J, Choi C, Park S, Choi D, Ha JW, Shin EC. Characterization of CD8(+)CD57(+) T cells in patients with acute myocardial infarction. Cell Mol Immunol. 2015;12(4):466–73.PubMedCrossRef
25.
Ilatovskaya DV, Pitts C, Clayton J, Domondon M, Troncoso M, Pippin S, DeLeon-Pennell KY. CD8(+) T-cells negatively regulate inflammation post-myocardial infarction. Am J Physiol Heart Circ Physiol. 2019;317(3):H581–96.PubMedPubMedCentralCrossRef
26.
27.
Silverio JC, Pereira IR, Cipitelli Mda C, Vinagre NF, Rodrigues MM, Gazzinelli RT, Lannes-Vieira J. CD8+ T-cells expressing interferon gamma or perforin play antagonistic roles in heart injury in experimental Trypanosoma cruzi-elicited cardiomyopathy. PLoS Pathog. 2012;8(4):e1002645.PubMedPubMedCentralCrossRef
28.
Vadasz Z, Elbirt D, Radian S, Bezalel-Rosenberg S, Mahlab-Guri K, Toubi E, Asher I, Sthoeger Z. Low levels of the immunoregulator Semaphorin 4D (CD100) in sera of HIV patients. Clin Immunol. 2018;191:88–93.PubMedCrossRef
29.
Correa-Rocha R, Lopez-Abente J, Gutierrez C, Perez-Fernandez VA, Prieto-Sanchez A, Moreno-Guillen S, Munoz-Fernandez MA, Pion M. CD72/CD100 and PD-1/PD-L1 markers are increased on T and B cells in HIV-1+ viremic individuals, and CD72/CD100 axis is correlated with T-cell exhaustion. PLoS One. 2018;13(8):e0203419.PubMedPubMedCentralCrossRef
30.
Liu B, Ma Y, Yi J, Xu Z, Zhang YS, Zhang C, Zhuang R, Yu H, Wang J, Yang A, et al. Elevated plasma soluble Sema4D/CD100 levels are associated with disease severity in patients of hemorrhagic fever with renal syndrome. PLoS One. 2013;8(9):e73958.PubMedPubMedCentralCrossRef
31.
Liu B, Ma Y, Zhang Y, Zhang C, Yi J, Zhuang R, Yu H, Yang A, Zhang Y, Jin B. CD8low CD100- T cells identify a novel CD8 T cell subset associated with viral control during human Hantaan virus infection. J Virol. 2015;89(23):11834–44.PubMedPubMedCentralCrossRef
32.
Gong H, Lyu X, Li S, Chen R, Hu M, Zhang X. sSema4D levels are increased in coronary heart disease and associated with the extent of coronary artery stenosis. Life Sci. 2019;219:329–35.PubMedCrossRef
33.
Li BJ, He Y, Zhang Y, Guo YH, Zhou Y, Zhang PX, Wang W, Zhao JR, Li JG, Zuo WZ, et al. Interferon-alpha-induced CD100 on naive CD8(+) T cells enhances antiviral responses to hepatitis C infection through CD72 signal transduction. J Int Med Res. 2017;45(1):89–100.PubMedPubMedCentralCrossRef
34.
Zhu L, Bergmeier W, Wu J, Jiang H, Stalker TJ, Cieslak M, Fan R, Boumsell L, Kumanogoh A, Kikutani H, et al. Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury. Proc Natl Acad Sci U S A. 2007;104(5):1621–6.PubMedPubMedCentralCrossRef
35.
Yoshida Y, Ogata A, Kang S, Ebina K, Shi K, Nojima S, Kimura T, Ito D, Morimoto K, Nishide M, et al. Semaphorin 4D contributes to rheumatoid arthritis by inducing inflammatory cytokine production: pathogenic and therapeutic implications. Arthritis Rheum. 2015;67(6):1481–90.CrossRef
36.
Basile JR, Holmbeck K, Bugge TH, Gutkind JS. MT1-MMP controls tumor-induced angiogenesis through the release of semaphorin 4D. J Biol Chem. 2007;282(9):6899–905.PubMedCrossRef
37.
Maleki KT, Cornillet M, Bjorkstrom NK. Soluble SEMA4D/CD100: a novel immunoregulator in infectious and inflammatory diseases. Clin Immunol. 2016;163:52–9.PubMedCrossRef
38.
Elhabazi A, Delaire S, Bensussan A, Boumsell L, Bismuth G. Biological activity of soluble CD100. I. the extracellular region of CD100 is released from the surface of T lymphocytes by regulated proteolysis. J Immunol. 2001;166(7):4341–7.PubMedCrossRef
39.
Zhou L, Kou DQ. Correlation between acute myocardial infarction complicated with cerebral infarction and expression levels of MMP-2 and MMP-9. Eur Rev Med Pharmacol Sci. 2019;23(1):297–302.PubMed
40.
Nakaya R, Uzui H, Shimizu H, Nakano A, Mitsuke Y, Yamazaki T, Ueda T, Lee JD. Pravastatin suppresses the increase in matrix metalloproteinase-2 levels after acute myocardial infarction. Int J Cardiol. 2005;105(1):67–73.PubMedCrossRef
41.
Ke Y, Dang E, Shen S, Zhang T, Qiao H, Chang Y, Liu Q, Wang G. Semaphorin4D drives CD8(+) T-cell Lesional trafficking in Oral lichen Planus via CXCL9/CXCL10 Upregulations in Oral keratinocytes. J Invest Dermatol. 2017;137(11):2396–406.PubMedCrossRef
42.
Boegel S, Lower M, Bukur T, Sahin U, Castle JC. A catalog of HLA type, HLA expression, and neo-epitope candidates in human cancer cell lines. Oncoimmunology. 2014;3(8):e954893.PubMedPubMedCentralCrossRef
Metadata
Title
CD100 modulates cytotoxicity of CD8+ T cells in patients with acute myocardial infarction
Authors
Yan Li
Li Qin
Qijun Bai
Jingjing Zhang
Ruixue Chen
Kunpeng Song
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2021
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/s12865-021-00406-y

Other articles of this Issue 1/2021

BMC Immunology 1/2021 Go to the issue

Research article

Direct effects of mast cell proteases, tryptase and chymase, on bronchial epithelial integrity proteins and anti-viral responses

Research

Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs)

Research

Phenotypic and immune functional profiling of patients with suspected Mendelian Susceptibility to Mycobacterial Disease in South Africa

Research article

Vaccinomic approach for novel multi epitopes vaccine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)

Research

Repression of the expression of proinflammatory genes by mitochondrial transcription factor A is linked to its alternative splicing regulation in human lung epithelial cells

Research

Optimizing interleukin-2 concentration, seeding density and bead-to-cell ratio of T-cell expansion for adoptive immunotherapy
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits