Download PDF
Thromb Haemost 2011; 106(05): 814-819
DOI: 10.1160/TH11-05-0336
Theme Issue Article
Schattauer GmbH

Natural killer T cells in lipoprotein metabolism and atherosclerosis

Godfrey S. Getz
1   Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
,
Paul A. VanderLaan
1   Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
,
Catherine A. Reardon
1   Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
› Author Affiliations Financial support: This work was supported by grants from the NHI Heart, Lung and Blood Institute (Grant No. HL088420) and the Foundation Leducq.
Further Information

Publication History

Received: 17 May 2011

Accepted after minor revision: 23 August 2011

Publication Date:
23 November 2017 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Cells of both the innate and adaptive immune system participate in the development of atherosclerosis, a chronic inflammatory disorder of medium and large arteries. Natural killer T (NKT) cells express surface markers characteristic of natural killer cells and conventional T cells and bridge the innate and adaptive immune systems. The development and activation of NKT cells is dependent upon CD1d, a MHC-class I-type molecule that presents lipids, especially glycolipids to the T cell receptors on NKT cells. There are two classes of NKT cells; invariant NKT cells that express a semi-invariant T cell receptor and variant NKT cells. This review summarises studies in murine models in which the effect of the activation, overexpression or deletion of NKT cells or only invariant NKT cells on atherosclerosis has been examined.

Keywords

Atherosclerosis - CD1d - NKT cells
 

  • References

  • 1 Packard RR, Lichtman AH, Libby P. Innate and adaptive immunity in atherosclerosis. Semin Immunopathol 2009; 31: 5-22.
    CrossrefPubMedGoogle Scholar
  • 2 Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Rev Immunol 2011; 3: 204-221.
    PubMedGoogle Scholar
  • 3 Getz GS, VanderLaan PA, Reardon CA. The immune system and murine atherosclerosis. Curr Drug Targets 2007; 8: 1297-1306.
    CrossrefPubMedGoogle Scholar
  • 4 Bendelac A, Savage PB, Teyton L. The biology of NKT cells. Annu Rev Immunol 2007; 25: 297-336.
    CrossrefPubMedGoogle Scholar
  • 5 Kronenberg M. Towards an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol 2005; 26: 877-900.
    PubMedGoogle Scholar
  • 6 Van Kaer L, Parekh VV, Wu L. Invariant natural killer T cells: bridging innate and adaptive immunity. Cell Tissue Res 2011; 343: 43-55.
    CrossrefPubMedGoogle Scholar
  • 7 Bobryshev YV, Lord RSA. Co-accumulation of dendritic cells and natural killer T cells within rupture-prone regions in human atherosclerotic plaques. J Histochem Cytochem 2005; 53: 781-785.
    CrossrefPubMedGoogle Scholar
  • 8 Garner B, Priestman DA, Stocker R. et al. Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice. J Lipid Res 2002; 43: 205-214.
    PubMedGoogle Scholar
  • 9 Kronenberg M, Gapin L. The unconventional lifestyle of NKT cells. Nat Rev Immunol 2002; 2: 557-568.
    CrossrefPubMedGoogle Scholar
  • 10 Berzins SP, Smyth MJ, Baxter AG. Presumed guilty: natural killer T cell defects and human disease. Nat Rev Immunol 2011; 11: 131-142.
    CrossrefPubMedGoogle Scholar
  • 11 Tupin E, Kinjo Y, Kronenberg M. The unique role of natural killer T cells in the response to microorganisms. Nat Rev Microbiol 2007; 5: 405-417.
    CrossrefPubMedGoogle Scholar
  • 12 Mallevaey T, Fontaine J, Breuilh L. et al. Invariant and noninvariant natural killer T cells exert opposite regulatory functions on the immune response during murine schistosomiasis. Infect Immun 2007; 75: 2171-2180.
    CrossrefPubMedGoogle Scholar
  • 13 Leadbetter EA, Brigl M, Illarionov P. et al. NK T cells provide lipid antigen-specific cognate help for B cells. Proc Natl Acad Sci USA 2008; 105: 8339-8344.
    CrossrefPubMedGoogle Scholar
  • 14 Lievens D, Eijgelaar WJ, Biessen EA. et al. The multi-functionality of CD40L and its receptor CD40 in atherosclerosis. Thromb Haemost 2009; 102: 206-214.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Gotsman I, Sharpe AH, Lichtman AH. T-cell costimulation and coinhibition in atherosclerosis. Circ Res 2008; 103: 1220-1231.
    CrossrefPubMedGoogle Scholar
  • 16 Kim S, Lalani S, Parekh VV, Wu L, Van Kaer L. Glycolipid ligands of invariant natural killer T cells as vaccine adjuvants. Expert Rev Vaccines. 2008; 7: 1519-1532.
    CrossrefPubMedGoogle Scholar
  • 17 Barral DC, Brenner MB. CD1 antigen presentation: how it works. Nat Rev Immunol 2007; 7: 929-41.
    CrossrefPubMedGoogle Scholar
  • 18 Zimmer MI, Nguyen HP, Wang B. et al. Polymorphisms in CD1d affect antigen presentation and the activation of CD1d-restricted T cells. Proc Natl Acad Sci USA 2009; 106: 1909-1914.
    CrossrefPubMedGoogle Scholar
  • 19 Yanaba K, Bouaziz JD, Haas KM. et al. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity 2008; 28: 639-650.
    CrossrefPubMedGoogle Scholar
  • 20 Dougan SK, Kaser A, Blumberg RS. CD1 expression on antigen-presenting cells. Curr Top Microbiol Immunol 2007; 314: 113-141.
    PubMedGoogle Scholar
  • 21 Lee WY, Moriarty TJ, Wong CH. et al. An intravascular immune response to Borrelia burgdorferi involves Kupffer cells and iNKT cells. Nat Immunol 2010; 11: 295-302.
    CrossrefPubMedGoogle Scholar
  • 22 Geissmann F, Cameron TO, Sidobre S. et al. Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids. PLoS Biol 2005; 3: e113
    CrossrefPubMedGoogle Scholar
  • 23 Lacasse J, Martin LH. Detection of CD1 mRNA in Paneth cells of the mouse intestine by in situ hybridization. J Histochem Cytochem. 1992; 40: 1527-1534.
    CrossrefPubMedGoogle Scholar
  • 24 Wingender G, Kronenberg M. Role of NKT cells in the digestive system: IV. The role of canonical natural killer T cells in mucosal immunity and infection. Am J Physiol Gastrointest Liver Physiol 2008; 294: G1-G8.
    CrossrefPubMedGoogle Scholar
  • 25 Nieuwenhuis EE, Matsumoto T, Lindenbergh D. et al. Cd1d-dependent regulation of bacterial colonization in the intestine of mice. J Clin Invest 2009; 119: 1241-1250.
    CrossrefPubMedGoogle Scholar
  • 26 Zhou D, Mattner J, Cantu C. 3rd,et al. Lysosomal glycosphingolipid recognition by NKT cells. Science 2004; 306: 1786-1789.
    CrossrefPubMedGoogle Scholar
  • 27 Speak AO, Salio M, Neville DC. et al. Implications for invariant natural killer T cell ligands due to the restricted presence of isoglobotrihexosylceramide in mammals. Proc Natl Acad Sci USA 2007; 104: 5971-5976.
    CrossrefPubMedGoogle Scholar
  • 28 Porubsky S, Speak AO, Luckow B. et al. Normal development and function of invariant natural killer T cells in mice with isoglobotrihexosylceramide (iGb3) deficiency. Proc Natl Acad Sci USA 2007; 104: 5977-5982.
    CrossrefPubMedGoogle Scholar
  • 29 VanderLaan PA, Reardon CA, Sagiv Y. et al. Characterization of the natural killer T-cell response in an adoptive transfer model of atherosclerosis. Am J Pathol 2007; 170: 1100-1107.
    CrossrefPubMedGoogle Scholar
  • 30 Shashkin P, Dragulev B, Ley K. Macrophage differentiation to foam cells. Curr Pharm Des 2005; 11: 3061-3072.
    CrossrefPubMedGoogle Scholar
  • 31 Liu Y, Teige A, Mondoc E. et al. Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates tissue-specific inflammation in mice. J Clin Invest 2011; 121: 249-264.
    CrossrefPubMedGoogle Scholar
  • 32 van den Elzen P, Garg S, León L. et al. Apolipoprotein-mediated pathways of lipid antigen presentation. Nature 2005; 437: 906-910.
    CrossrefPubMedGoogle Scholar
  • 33 Allan LL, Hoefl K, Zheng DJ. et al. Apolipoprotein-mediated lipid antigen presentation in B cells provides a pathway for innate help by NKT cells. Blood 2009; 114: 2411-2416.
    CrossrefPubMedGoogle Scholar
  • 34 Miller YI, Viriyakosol S, Worrall DS. et al. Toll-like receptor 4-dependent and -independent cytokine secretion induced by minimally oxidized low-density lipoprotein in macrophages. Arterioscler Thromb Vasc Biol 2005; 25: 1213-1219.
    CrossrefPubMedGoogle Scholar
  • 35 Braun NA, Mendez-Fernandez YV, Covarrubias R. et al. Development of spontaneous anergy in invariant natural killer T cells in a mouse model of dyslipidemia. Arterioscler Thromb Vasc Biol 2010; 30: 1758-1765.
    CrossrefPubMedGoogle Scholar
  • 36 Nakai Y, Iwabuchi K, Fujii S. et al. Natural killer T cells accelerate atherogenesis in mice. Blood 2004; 104: 2051-2059.
    CrossrefPubMedGoogle Scholar
  • 37 Tupin E, Nicoletti A, Elhage R. et al. CD1d-dependent activation of NKT cells aggravates atherosclerosis. J Exp Med 2004; 199: 417-422.
    CrossrefPubMedGoogle Scholar
  • 38 van Puijvelde GH, van Wanrooij EJ, Hauer AD. et al. Effect of natural killer T cell activation on the initiation of atherosclerosis. Thromb Haemost 2009; 102: 223-230.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Major AS, Wilson MT, McCaleb JL. et al. Quantitative and qualitative differences in proatherogenic NKT cells in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2004; 24: 2351-2357.
    CrossrefPubMedGoogle Scholar
  • 40 Bendelac A, Henniker RD, Lantz O. Increased interleukin 4 and immunoglobulin E production in transgenic mice over expressing NK1 T cells. J Exp Med 1996; 184: 1285-1293.
    CrossrefPubMedGoogle Scholar
  • 41 Reardon CA, Blachowicz L, Lukens J. et al. Genetic background selectively influences innominate artery atherosclerosis: immune system deficiency as a probe. Arterioscler Thromb Vasc Biol 2003; 23: 1449-1454.
    CrossrefPubMedGoogle Scholar
  • 42 Reardon CA, Blachowicz L, White T. et al. Effect of immune deficiency on lipoproteins and atherosclerosis in male apoprotein E deficient mice. Arterioscler Thromb Vasc Biol 2001; 21: 1011-1016.
    CrossrefPubMedGoogle Scholar
  • 43 Aslanian AM, Chapman HA, Charo IF. Transient role for CD1d-restricted natural killer T cells in the formation of atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2005; 25: 628-632.
    CrossrefPubMedGoogle Scholar
  • 44 Mendiratta SK, Martin WD, Hong S. et al. CD1d1 mutant mice are deficient in natural T cells that promptly produce IL-4. Immunity 1997; 6: 469-477.
    CrossrefPubMedGoogle Scholar
  • 45 Chen YH, Chiu NM, Manual M. et al. Impaired NK1+ T cell development and early IL-4 production in CD1- deficient mice. Immunity 1997; 6: 459-467.
    CrossrefPubMedGoogle Scholar
  • 46 Rogers L, Burchat S, Gage J. et al. Deficiency of invariant Vα14 natural killer T cells decreases atherosclerosis in LDL receptor null mice. Cardiovasc Res 2008; 78: 167-174.
    CrossrefPubMedGoogle Scholar
  • 47 Berzofsky JA, Terabe M. The contrasting roles of NKT cells in tumor immunity. Curr Mol Med 2009; 9: 667-672.
    CrossrefPubMedGoogle Scholar
  • 48 Binder CJ. Natural IgM antibodies against oxidation-specific epitopes. J Clin Immunol 2010; 30 (Suppl. 01) S56-60.
    CrossrefPubMedGoogle Scholar
  • 49 Bouaziz JD, Yanaba K, Tedder FR. Regulatory B cells as inhibitors of immune responses and inflammation. Immunol Rev 2008; 224: 201-244.
    CrossrefPubMedGoogle Scholar
  • 50 Felio K, Nguyen H, Dascher CC. et al. CD1-restricted adaptive immune responses to Mycobacteria in human group 1 CD1 transgenic mice. J Exp Med 2009; 206: 2497-2499.
    CrossrefPubMedGoogle Scholar