Skip to main content
Erschienen in: Inflammation 1/2017

24.10.2016 | ORIGINAL ARTICLE

Reconfiguration of NKT Cell Subset Compartment Is Associated with Plaque Development in Patients with Carotid Artery Stenosis

verfasst von: Lun Cai, Lei Yu, Sa Liu, Tongxun Li, Xiaoping Zhang, Wei Cui, Jie Du, Qinyi Zhang

Erschienen in: Inflammation | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

Accumulating evidence shows that immune cells play an important role in carotid atherosclerotic plaque development. In this study, we assessed the association of 6 different natural killer T (NKT) cell subsets, based on CD57 and CD8 expression, with risk for development of carotid atherosclerotic plaque (CAP). Molecular expression by peripheral NKT cells was evaluated in 13 patients with high-risk CAP and control without carotid stenosis (n = 18). High-risk CAP patients, compared with healthy subjects, had less percentage of CD57+CD8− NKT cell subsets (8.64 ± 10.15 versus 19.62 ± 10.8 %; P = 0.01) and CD57+CD8int NKT cell subsets (4.32 ± 3.04 versus 11.87 ± 8.56 %; P = 0.002), with a corresponding increase in the CD57−CD8high NKT cell subsets (33.22 ± 11.87 versus 18.66 ± 13.68 %; P = 0.007). Intracellular cytokine staining showed that CD8+ NKT cell subset was the main cytokine-producing NKT cell. Cytokine production in plasma was measured with Bio-Plex assay. The expression levels of pro-inflammatory mediators (IFN-γ, IL-17, IP-10) were significantly higher in CAP patients as compared to that from controls. These data provide evidence that NKT cell subset compartment reconfiguration in patients with carotid stenosis seems to be associated with the occurrence of carotid atherosclerotic plaque and suggest that both pathogenic and protective NKT cell subsets exist.
Literatur
1.
Zurück zum Zitat Mathers, C.D., T. Boerma, and Fat D. Ma. 2009. Global and regional causes of death. British Medical Bulletin 92: 7–32.CrossRefPubMed Mathers, C.D., T. Boerma, and Fat D. Ma. 2009. Global and regional causes of death. British Medical Bulletin 92: 7–32.CrossRefPubMed
2.
Zurück zum Zitat Hansson, G.K., and A. Hermansson. 2011. The immune system in atherosclerosis. Nature Immunology 12: 204–212.CrossRefPubMed Hansson, G.K., and A. Hermansson. 2011. The immune system in atherosclerosis. Nature Immunology 12: 204–212.CrossRefPubMed
3.
Zurück zum Zitat Pitocco, D., S. Giubilato, F. Zaccardi, E. Di Stasio, A. Buffon, L.M. Biasucci, et al. 2009. Pioglitazone reduces monocyte activation in type 2 diabetes. Acta Diabetologica 46: 75–77.CrossRefPubMed Pitocco, D., S. Giubilato, F. Zaccardi, E. Di Stasio, A. Buffon, L.M. Biasucci, et al. 2009. Pioglitazone reduces monocyte activation in type 2 diabetes. Acta Diabetologica 46: 75–77.CrossRefPubMed
4.
Zurück zum Zitat Hansson, G.K. 2005. Inflammation, atherosclerosis, and coronary artery disease. New England Journal of Medicine 352: 1685–1695.CrossRefPubMed Hansson, G.K. 2005. Inflammation, atherosclerosis, and coronary artery disease. New England Journal of Medicine 352: 1685–1695.CrossRefPubMed
5.
Zurück zum Zitat Ciccone, M.M., A. Marzullo, D. Mizio, D. Angiletta, F. Cortese, P. Scicchitano, et al. 2011. Can carotid plaque histology selectively predict the risk of an acute coronary syndrome? International Heart Journal 52: 72–77.CrossRefPubMed Ciccone, M.M., A. Marzullo, D. Mizio, D. Angiletta, F. Cortese, P. Scicchitano, et al. 2011. Can carotid plaque histology selectively predict the risk of an acute coronary syndrome? International Heart Journal 52: 72–77.CrossRefPubMed
6.
Zurück zum Zitat Xia, Q., X. Xiang, S. Patel, R. Puranik, Q. Xie, and S. Bao. 2012. Characterisation of IL-22 and interferon-gamma-inducible chemokines in human carotid plaque. International Journal of Cardiology 154: 187–189.CrossRefPubMed Xia, Q., X. Xiang, S. Patel, R. Puranik, Q. Xie, and S. Bao. 2012. Characterisation of IL-22 and interferon-gamma-inducible chemokines in human carotid plaque. International Journal of Cardiology 154: 187–189.CrossRefPubMed
7.
Zurück zum Zitat Van Der Vliet, H.J., N. Nishi, Y. Koezuka, M.A. Peyrat, B.M. Von Blomberg, A.J. Van Den Eertwegh, et al. 1999. Effects of alpha-galactosylceramide (KRN7000), interleukin-12 and interleukin-7 on phenotype and cytokine profile of human Valpha24+ Vbeta11+ T cells. Immunology 98: 557–563.CrossRefPubMedPubMedCentral Van Der Vliet, H.J., N. Nishi, Y. Koezuka, M.A. Peyrat, B.M. Von Blomberg, A.J. Van Den Eertwegh, et al. 1999. Effects of alpha-galactosylceramide (KRN7000), interleukin-12 and interleukin-7 on phenotype and cytokine profile of human Valpha24+ Vbeta11+ T cells. Immunology 98: 557–563.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Vivier, E., and N. Anfossi. 2004. Inhibitory NK-cell receptors on T cells: witness of the past, actors of the future. Nature Reviews Immunology 4: 190–198.CrossRefPubMed Vivier, E., and N. Anfossi. 2004. Inhibitory NK-cell receptors on T cells: witness of the past, actors of the future. Nature Reviews Immunology 4: 190–198.CrossRefPubMed
9.
Zurück zum Zitat Braunersreuther, V., F. Mach, and S. Steffens. 2007. The specific role of chemokines in atherosclerosis. Thrombosis and Haemostasis 97: 714–721.PubMed Braunersreuther, V., F. Mach, and S. Steffens. 2007. The specific role of chemokines in atherosclerosis. Thrombosis and Haemostasis 97: 714–721.PubMed
10.
Zurück zum Zitat Profumo, E., A. Siracusano, E. Ortona, P. Margutti, A. Carra, A. Costanzo, et al. 2003. Cytokine expression in circulating T lymphocytes from patients undergoing carotid endarterectomy. The Journal of Cardiovascular Surgery 44: 237–242.PubMed Profumo, E., A. Siracusano, E. Ortona, P. Margutti, A. Carra, A. Costanzo, et al. 2003. Cytokine expression in circulating T lymphocytes from patients undergoing carotid endarterectomy. The Journal of Cardiovascular Surgery 44: 237–242.PubMed
11.
Zurück zum Zitat Li, Y., K. To, P. Kanellakis, H. Hosseini, V. Deswaerte, P. Tipping, et al. 2015. CD4+ natural killer T cells potently augment aortic root atherosclerosis by perforin- and granzyme B-dependent cytotoxicity. Circulation Research 116: 245–254.CrossRefPubMed Li, Y., K. To, P. Kanellakis, H. Hosseini, V. Deswaerte, P. Tipping, et al. 2015. CD4+ natural killer T cells potently augment aortic root atherosclerosis by perforin- and granzyme B-dependent cytotoxicity. Circulation Research 116: 245–254.CrossRefPubMed
12.
Zurück zum Zitat Subramanian, S., M.S. Turner, Y. Ding, L. Goodspeed, S. Wang, J.H. Buckner, et al. 2013. Increased levels of invariant natural killer T lymphocytes worsen metabolic abnormalities and atherosclerosis in obese mice. Journal of Lipid Research 54: 2831–2841.CrossRefPubMedPubMedCentral Subramanian, S., M.S. Turner, Y. Ding, L. Goodspeed, S. Wang, J.H. Buckner, et al. 2013. Increased levels of invariant natural killer T lymphocytes worsen metabolic abnormalities and atherosclerosis in obese mice. Journal of Lipid Research 54: 2831–2841.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Kyriakakis, E., M. Cavallari, J. Andert, M. Philippova, C. Koella, V. Bochkov, et al. 2010. Invariant natural killer T cells: linking inflammation and neovascularization in human atherosclerosis. European Journal of Immunology 40: 3268–3279.CrossRefPubMed Kyriakakis, E., M. Cavallari, J. Andert, M. Philippova, C. Koella, V. Bochkov, et al. 2010. Invariant natural killer T cells: linking inflammation and neovascularization in human atherosclerosis. European Journal of Immunology 40: 3268–3279.CrossRefPubMed
14.
Zurück zum Zitat Bobryshev, Y.V., and R.S. Lord. 2005. Co-accumulation of dendritic cells and natural killer T cells within rupture-prone regions in human atherosclerotic plaques. Journal of Histochemistry and Cytochemistry 53: 781–785.CrossRefPubMed Bobryshev, Y.V., and R.S. Lord. 2005. Co-accumulation of dendritic cells and natural killer T cells within rupture-prone regions in human atherosclerotic plaques. Journal of Histochemistry and Cytochemistry 53: 781–785.CrossRefPubMed
15.
Zurück zum Zitat Smyth, M.J., M.E. Wallace, S.L. Nutt, H. Yagita, D.I. Godfrey, and Y. Hayakawa. 2005. Sequential activation of NKT cells and NK cells provides effective innate immunotherapy of cancer. Journal of Experimental Medicine 201: 1973–1985.CrossRefPubMedPubMedCentral Smyth, M.J., M.E. Wallace, S.L. Nutt, H. Yagita, D.I. Godfrey, and Y. Hayakawa. 2005. Sequential activation of NKT cells and NK cells provides effective innate immunotherapy of cancer. Journal of Experimental Medicine 201: 1973–1985.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Eberl, G., and H.R. MacDonald. 2000. Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells. European Journal of Immunology 30: 985–992.CrossRefPubMed Eberl, G., and H.R. MacDonald. 2000. Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells. European Journal of Immunology 30: 985–992.CrossRefPubMed
17.
Zurück zum Zitat Kim, C.H., B. Johnston, and E.C. Butcher. 2002. Trafficking machinery of NKT cells: shared and differential chemokine receptor expression among V alpha 24(+)V beta 11(+) NKT cell subsets with distinct cytokine-producing capacity. Blood 100: 11–16.CrossRefPubMed Kim, C.H., B. Johnston, and E.C. Butcher. 2002. Trafficking machinery of NKT cells: shared and differential chemokine receptor expression among V alpha 24(+)V beta 11(+) NKT cell subsets with distinct cytokine-producing capacity. Blood 100: 11–16.CrossRefPubMed
18.
Zurück zum Zitat Gumperz, J.E., S. Miyake, T. Yamamura, and M.B. Brenner. 2002. Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. Journal of Experimental Medicine 195: 625–636.CrossRefPubMedPubMedCentral Gumperz, J.E., S. Miyake, T. Yamamura, and M.B. Brenner. 2002. Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. Journal of Experimental Medicine 195: 625–636.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Montoya, C.J., D. Pollard, J. Martinson, K. Kumari, C. Wasserfall, C.B. Mulder, et al. 2007. Characterization of human invariant natural killer T subsets in health and disease using a novel invariant natural killer T cell-clonotypic monoclonal antibody, 6B11. Immunology 122: 1–14.CrossRefPubMedPubMedCentral Montoya, C.J., D. Pollard, J. Martinson, K. Kumari, C. Wasserfall, C.B. Mulder, et al. 2007. Characterization of human invariant natural killer T subsets in health and disease using a novel invariant natural killer T cell-clonotypic monoclonal antibody, 6B11. Immunology 122: 1–14.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Godfrey, D.I., S. Stankovic, and A.G. Baxter. 2010. Raising the NKT cell family. Nature Immunology 11: 197–206.CrossRefPubMed Godfrey, D.I., S. Stankovic, and A.G. Baxter. 2010. Raising the NKT cell family. Nature Immunology 11: 197–206.CrossRefPubMed
21.
Zurück zum Zitat Major, A.S., S. Joyce, and L. Van Kaer. 2006. Lipid metabolism, atherogenesis and CD1-restricted antigen presentation. Trends in Molecular Medicine 12: 270–278.CrossRefPubMed Major, A.S., S. Joyce, and L. Van Kaer. 2006. Lipid metabolism, atherogenesis and CD1-restricted antigen presentation. Trends in Molecular Medicine 12: 270–278.CrossRefPubMed
22.
Zurück zum Zitat Tupin, E., A. Nicoletti, R. Elhage, M. Rudling, H.G. Ljunggren, G.K. Hansson, et al. 2004. CD1d-dependent activation of NKT cells aggravates atherosclerosis. Journal of Experimental Medicine 199: 417–422.CrossRefPubMedPubMedCentral Tupin, E., A. Nicoletti, R. Elhage, M. Rudling, H.G. Ljunggren, G.K. Hansson, et al. 2004. CD1d-dependent activation of NKT cells aggravates atherosclerosis. Journal of Experimental Medicine 199: 417–422.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat To, K., A. Agrotis, G. Besra, A. Bobik, and B.H. Toh. 2009. NKT cell subsets mediate differential proatherogenic effects in ApoE−/− mice. Arteriosclerosis, Thrombosis, and Vascular Biology 29: 671–677.CrossRefPubMed To, K., A. Agrotis, G. Besra, A. Bobik, and B.H. Toh. 2009. NKT cell subsets mediate differential proatherogenic effects in ApoE−/− mice. Arteriosclerosis, Thrombosis, and Vascular Biology 29: 671–677.CrossRefPubMed
24.
Zurück zum Zitat Coquet, J.M., K. Kyparissoudis, D.G. Pellicci, G. Besra, S.P. Berzins, M.J. Smyth, et al. 2007. IL-21 is produced by NKT cells and modulates NKT cell activation and cytokine production. Journal of Immunology 178: 2827–2834.CrossRef Coquet, J.M., K. Kyparissoudis, D.G. Pellicci, G. Besra, S.P. Berzins, M.J. Smyth, et al. 2007. IL-21 is produced by NKT cells and modulates NKT cell activation and cytokine production. Journal of Immunology 178: 2827–2834.CrossRef
25.
Zurück zum Zitat Davenport, P., and P.G. Tipping. 2003. The role of interleukin-4 and interleukin-12 in the progression of atherosclerosis in apolipoprotein E-deficient mice. American Journal of Pathology 163: 1117–1125.CrossRefPubMedPubMedCentral Davenport, P., and P.G. Tipping. 2003. The role of interleukin-4 and interleukin-12 in the progression of atherosclerosis in apolipoprotein E-deficient mice. American Journal of Pathology 163: 1117–1125.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Gupta, S., A.M. Pablo, X. Jiang, N. Wang, A.R. Tall, and C. Schindler. 1997. IFN-gamma potentiates atherosclerosis in ApoE knock-out mice. Journal of Clinical Investigation 99: 2752–2761.CrossRefPubMedPubMedCentral Gupta, S., A.M. Pablo, X. Jiang, N. Wang, A.R. Tall, and C. Schindler. 1997. IFN-gamma potentiates atherosclerosis in ApoE knock-out mice. Journal of Clinical Investigation 99: 2752–2761.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Erbel, C., T.J. Dengler, S. Wangler, F. Lasitschka, F. Bea, N. Wambsganss, et al. 2011. Expression of IL-17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability. Basic Research in Cardiology 106: 125–134.CrossRefPubMed Erbel, C., T.J. Dengler, S. Wangler, F. Lasitschka, F. Bea, N. Wambsganss, et al. 2011. Expression of IL-17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability. Basic Research in Cardiology 106: 125–134.CrossRefPubMed
28.
Zurück zum Zitat Ammirati, E., D. Cianflone, M. Banfi, V. Vecchio, A. Palini, M. De Metrio, et al. 2010. Circulating CD4+CD25hiCD127lo regulatory T-Cell levels do not reflect the extent or severity of carotid and coronary atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology 30: 1832–1841.CrossRefPubMed Ammirati, E., D. Cianflone, M. Banfi, V. Vecchio, A. Palini, M. De Metrio, et al. 2010. Circulating CD4+CD25hiCD127lo regulatory T-Cell levels do not reflect the extent or severity of carotid and coronary atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology 30: 1832–1841.CrossRefPubMed
29.
Zurück zum Zitat Yamamoto, S., P.G. Yancey, Y. Zuo, L.J. Ma, R. Kaseda, A.B. Fogo, et al. 2011. Macrophage polarization by angiotensin II-type 1 receptor aggravates renal injury-acceleration of atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology 31: 2856–2864.CrossRefPubMedPubMedCentral Yamamoto, S., P.G. Yancey, Y. Zuo, L.J. Ma, R. Kaseda, A.B. Fogo, et al. 2011. Macrophage polarization by angiotensin II-type 1 receptor aggravates renal injury-acceleration of atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology 31: 2856–2864.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Nicholls, S.J., E.M. Tuzcu, K. Wolski, O. Bayturan, A. Lavoie, K. Uno, et al. 2011. Lowering the triglyceride/high-density lipoprotein cholesterol ratio is associated with the beneficial impact of pioglitazone on progression of coronary atherosclerosis in diabetic patients: insights from the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) study. Journal of the American College of Cardiology 57: 153–159.CrossRefPubMed Nicholls, S.J., E.M. Tuzcu, K. Wolski, O. Bayturan, A. Lavoie, K. Uno, et al. 2011. Lowering the triglyceride/high-density lipoprotein cholesterol ratio is associated with the beneficial impact of pioglitazone on progression of coronary atherosclerosis in diabetic patients: insights from the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) study. Journal of the American College of Cardiology 57: 153–159.CrossRefPubMed
31.
Zurück zum Zitat Saremi, A., D.C. Schwenke, T.A. Buchanan, H.N. Hodis, W.J. Mack, M. Banerji, et al. 2013. Pioglitazone slows progression of atherosclerosis in prediabetes independent of changes in cardiovascular risk factors. Arteriosclerosis, Thrombosis, and Vascular Biology 33: 393–399.CrossRefPubMed Saremi, A., D.C. Schwenke, T.A. Buchanan, H.N. Hodis, W.J. Mack, M. Banerji, et al. 2013. Pioglitazone slows progression of atherosclerosis in prediabetes independent of changes in cardiovascular risk factors. Arteriosclerosis, Thrombosis, and Vascular Biology 33: 393–399.CrossRefPubMed
32.
Zurück zum Zitat Babaev, V.R., P.G. Yancey, S.V. Ryzhov, V. Kon, M.D. Breyer, M.A. Magnuson, et al. 2005. Conditional knockout of macrophage PPARgamma increases atherosclerosis in C57BL/6 and low-density lipoprotein receptor-deficient mice. Arteriosclerosis, Thrombosis, and Vascular Biology 25: 1647–1653.CrossRefPubMed Babaev, V.R., P.G. Yancey, S.V. Ryzhov, V. Kon, M.D. Breyer, M.A. Magnuson, et al. 2005. Conditional knockout of macrophage PPARgamma increases atherosclerosis in C57BL/6 and low-density lipoprotein receptor-deficient mice. Arteriosclerosis, Thrombosis, and Vascular Biology 25: 1647–1653.CrossRefPubMed
Metadaten
Titel
Reconfiguration of NKT Cell Subset Compartment Is Associated with Plaque Development in Patients with Carotid Artery Stenosis
verfasst von
Lun Cai
Lei Yu
Sa Liu
Tongxun Li
Xiaoping Zhang
Wei Cui
Jie Du
Qinyi Zhang
Publikationsdatum
24.10.2016
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 1/2017
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-016-0456-6

Weitere Artikel der Ausgabe 1/2017

Inflammation 1/2017 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.