Skip to main content
SpringerLink
Log in

Harnessing NKT Cells for Therapeutic Applications

  • Chapter
T Cell Activation by CD1 and Lipid Antigens

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 314))

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Bezbradica JS, Stanic AK, Matsuki N, Bour-Jordan H, Bluestone JA, Thomas JW, Unutmaz D, Van Kaer L, Joyce S (2005) Distinct roles of dendritic cells and B cells in Va14Ja18 natural T cell activation in vivo. J Immunol 174:4696–4705

    PubMed  CAS  Google Scholar 

  • Brigl M, Bry L, Kent SC, Gumperz JE, Brenner MB (2003) Mechanism of CD1d-restricted natural killer T cell activation during microbial infection. Nat Immunol 4:1230–1237

    Article  PubMed  CAS  Google Scholar 

  • Cardell SL (2006) The natural killer T lymphocyte: a player in the complex regulation of autoimmune diabetes in non-obese diabetic mice. Clin Exp Immunol 143:194–202

    Article  PubMed  CAS  Google Scholar 

  • Carnaud C, Lee D, Donnars O, Park SH, Beavis A, Koezuka Y, Bendelac A (1999) Cutting edge: cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol 163:4647–4650

    PubMed  CAS  Google Scholar 

  • Chang DH, Osman K, Connolly J, Kukreja A, Krasovsky J, Pack M, Hutchinson A, Geller M, Liu N, Annable R et al (2005) Sustained expansion of NKT cells and antigen-specific T cells after injection of alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients. J Exp Med 201:1503–1517

    Article  PubMed  CAS  Google Scholar 

  • Chen JL, Stewart-Jones G, Bossi G, Lissin NM, Wooldridge L, Choi EM, Held G, Dunbar PR, Esnouf RM, Sami M et al (2005) Structural and kinetic basis for heightened immunogenicity of T cell vaccines. J Exp Med 201:1243–1255

    Article  PubMed  CAS  Google Scholar 

  • Chen YG, Choisy-Rossi CM, Holl TM, Chapman HD, Besra GS, Porcelli SA, Shaffer DJ, Roopenian D, Wilson SB, Serreze DV (2005) Activated NKT cells inhibit autoimmune diabetes through tolerogenic recruitment of dendritic cells to pancreatic lymph nodes. J Immunol 174:1196–1204

    PubMed  CAS  Google Scholar 

  • Chung Y, Chang WS, Kim S, Kang CY (2004) NKT cell ligand alpha-galactosylceramide blocks the induction of oral tolerance by triggering dendritic cell maturation. Eur J Immunol 34:2471–2479

    Article  PubMed  CAS  Google Scholar 

  • Crowe NY, Coquet JM, Berzins SP, Kyparissoudis K, Keating R, Pellicci DG, Hayakawa Y, Godfrey DI, Smyth MJ (2005) Differential antitumor immunity mediated by NKT cell subsets in vivo. J Exp Med 202:1279–1288

    Article  PubMed  CAS  Google Scholar 

  • Cui J, Shin T, Kawano T, Sato H, Kondo E, Toura I, Kaneko Y, Koseki H, Kanno M, Taniguchi M (1997) Requirement for Valpha14. NKT cells in IL-12-mediated rejection of tumors. Science 278:1623–1626

    Article  PubMed  CAS  Google Scholar 

  • Donnelly JJ, Wahren B, Liu MA (2005) DNA vaccines: progress and challenges. J Immunol 175:633–639

    PubMed  CAS  Google Scholar 

  • Ercolini AM, Miller SD (2006) Mechanisms of immunopathology in murine models of central nervous system demyelinating disease. J Immunol 176:3293–3298

    PubMed  CAS  Google Scholar 

  • Exley MA, Tahir SM, Cheng O, Shaulov A, Joyce R, Avigan D, Sackstein R, Balk SP (2001) A major fraction of human bone marrow lymphocytes are Th2-like CD1d-reactive T cells that can suppress mixed lymphocyte responses. J Immunol 167:5531–5534

    PubMed  CAS  Google Scholar 

  • Fujii S, Shimizu K, Kronenberg M, Steinman RM (2002) Prolonged IFN-gamma-producing NKT response induced with alpha-galactosylceramide-loaded DCs. Nat Immunol 3:867–874

    Article  PubMed  CAS  Google Scholar 

  • Fujii S, Shimizu K, Smith C, Bonifaz L, Steinman RM (2003) Activation of natural killer T cells by alpha-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8. T cell immunity to a coadministered protein. J Exp Med 198:267–279

    Article  PubMed  CAS  Google Scholar 

  • Fujii S, Liu K, Smith C, Bonito AJ, Steinman RM (2004) The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation. J Exp Med 199:1607–1618

    Article  PubMed  CAS  Google Scholar 

  • Gadola SD, Dulphy N, Salio M, Cerundolo V (2002) Valpha24-JalphaQ-independent CD1d-restricted recognition of alpha-galactosylceramide by human CD4(+) and CD8alphabeta(+) T lymphocytes. J Immunol 168:5514–5520

    PubMed  CAS  Google Scholar 

  • Gadola SD, Koch M, Marles-Wright J, Lissin NM, Shepherd D, Matulis G, Harlos K, Villiger PM, Stuart DI, Jakobsen BK et al (2006) Structure and binding kinetics of three different human CD1d-alpha-galactosylceramide-specific T cell receptors. J Exp Med 203:699–710

    Article  PubMed  CAS  Google Scholar 

  • Galli G, Nuti S, Tavarini S, Galli-Stampino L, De Lalla C, Casorati G, Dellabona P, Abrignani S (2003) CD1d-restricted help to B cells by human invariant natural killer T lymphocytes. J Exp Med 197:1051–1057

    Article  PubMed  CAS  Google Scholar 

  • Giaccone G (2002) A phase I study of the natural killer T-cell ligand alpha-galactosylceramide in patients with solid tumors. Clin Cancer Res 8:3702–3709

    PubMed  CAS  Google Scholar 

  • Godfrey DI, Kronenberg M (2004) Going both ways: immune regulation via CD1d-dependent NKT cells. J Clin Invest 114:1379–1388

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez-Aseguinolaza G, Van Kaer L, Bergmann CC, Wilson JM, Schmieg J, Kronenberg M, Nakayama T, Taniguchi M, Koezuka Y, Tsuji M (2002) Natural killer T cell ligand alpha-galactosylceramide enhances protective immunity induced by malaria vaccines. J Exp Med 195:617–624

    Article  PubMed  CAS  Google Scholar 

  • Gumperz JE, Miyake S, Yamamura T, Brenner MB (2002) Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. J Exp Med 195:625–636

    Article  PubMed  CAS  Google Scholar 

  • Haraguchi K, Takahashi T, Hiruma K, Kanda Y, Tanaka Y, Ogawa S, Chiba S, Miura O, Sakamaki H, Hirai H (2004) Recovery of Valpha24+ NKT cells after hematopoietic stem cell transplantation. Bone Marrow Transplant 34:595–602

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto D, Asakura S, Miyake S, Yamamura T, Van Kaer L, Liu C, Tanimoto M, Teshima T (2005) Stimulation of host NKT cells by synthetic glycolipid regulates acute graft-versus-host disease by inducing Th2 polarization of donor T cells. J Immunol 174:551–556

    PubMed  CAS  Google Scholar 

  • Hayakawa Y, Takeda K, Yagita H, Kakuta S, Iwakura Y, Van Kaer L, Saiki I, Okumura K (2001) Critical contribution of IFN-gamma and NK cells, but not perforin-mediated cytotoxicity, to anti-metastatic effect of alpha-galactosylceramide. Eur J Immunol 31:1720–1727

    Article  PubMed  CAS  Google Scholar 

  • Hermans IF, Silk JD, Gileadi U, Salio M, Mathew B, Ritter G, Schmidt R, Harris AL, Old L, Cerundolo V (2003) NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells. J Immunol 171:5140–5147

    PubMed  CAS  Google Scholar 

  • Hermans IF, Silk JD, Gileadi U, Masri SH, Shepherd D, Farrand KJ, Salio M, Cerundolo V (2007) Dendritic cell function can be modulated through cooperatve actions of TLR ligands and invariant NKT cells. J Immunol 178:2721–2729

    PubMed  CAS  Google Scholar 

  • Jahng A, Maricic I, Aguilera C, Cardell S, Halder RC, Kumar V (2004) Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide. J Exp Med 199:947–957

    Article  PubMed  CAS  Google Scholar 

  • Kim CH, Johnston B, Butcher EC (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

    Article  PubMed  CAS  Google Scholar 

  • Kinjo Y, Wu D, Kim G, Xing GW, Poles MA, Ho DD, Tsuji M, Kawahara K, Wong CH, Kronenberg M (2005) Recognition of bacterial glycosphingolipids by natural killer T cells. Nature 434:520–525

    Article  PubMed  CAS  Google Scholar 

  • Kjer-Nielsen L, Borg NA, Pellicci DG, Beddoe T, Kostenko L, Clements CS, Williamson NA, Smyth MJ, Besra GS, Reid HH et al (2006) A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition. J Exp Med 203:661–673

    Article  PubMed  CAS  Google Scholar 

  • Ko SY, Ko HJ, Chang WS, Park SH, Kweon MN, Kang CY (2005) Alpha-galactosylceramide can act as a nasal vaccine adjuvant inducing protective immune responses against viral infection and tumor. J Immunol 175:3309–3317

    PubMed  CAS  Google Scholar 

  • Koch M, Stronge VS, Shepherd D, Gadola SD, Mathew B, Ritter G, Fersht AR, Besra GS, Schmidt RR, Jones EY, Cerundolo V (2005) The crystal structure of human CD1d with and without alpha-galactosylceramide. Nat Immunol 6:819–826

    Article  PubMed  CAS  Google Scholar 

  • Kojo S, Seino K, Harada M, Watarai H, Wakao H, Uchida T, Nakayama T, Taniguchi M (2005) Induction of regulatory properties in dendritic cells by Valpha 14. NKT cells. J Immunol 175:3648–3655

    PubMed  CAS  Google Scholar 

  • Lee PT, Benlagha K, Teyton L, Bendelac A (2002) Distinct functional lineages of human V(alpha)24 natural killer T cells. J Exp Med 195:637–641

    Article  PubMed  CAS  Google Scholar 

  • Liu K, Idoyaga J, Charalambous A, Fujii S, Bonito A, Mordoh J, Wainstok R, Bai XF, Liu Y, Steinman RM (2005) Innate NKT lymphocytes confer superior adaptive immunity via tumor-capturing dendritic cells. J Exp Med 202:1507–1516

    Article  PubMed  CAS  Google Scholar 

  • Marschner A, Rothenfusser S, Hornung V, Prell D, Krug A, Kerkmann M, Wellisch D, Poeck H, Greinacher A, Giese T et al (2005) CpGODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells. Eur J Immunol 35:2347–2357

    Article  PubMed  CAS  Google Scholar 

  • Mattner J, Debord KL, Ismail N, Goff RD, Cantu C 3rd, Zhou D, Saint-Mezard P, Wang V, Gao Y, Yin N et al (2005) Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434:525–529

    Article  PubMed  CAS  Google Scholar 

  • Miyake S, Yamamura T (2005) Therapeutic potential of glycolipid ligands for natural killer (NK) T cells in the suppression of autoimmune diseases. Curr Drug Targets Immune Endocr Metabol Disord 5:315–322

    Article  PubMed  CAS  Google Scholar 

  • Miyamoto K, Miyake S, Yamamura T (2001) A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH2 bias of natural killer T cells. Nature 413:531–534

    Article  PubMed  CAS  Google Scholar 

  • Morris ES, MacDonald KP, Rowe V, Banovic T, Kuns RD, Don AL, Bofinger HM, Burman AC, Olver SD, Kienzle N et al (2005) NKT cell-dependent leukemia eradication following stem cell mobilization with potent G-CSF analogs. J Clin Invest 115:3093–3103

    Article  PubMed  CAS  Google Scholar 

  • Naumov YN, Bahjat KS, Gausling R, Abraham R, Exley MA, Koezuka Y, Balk SB, Strominger JL, Clare-Salzer M, Wilson SB (2001) Activation of CD1d-restricted T cells protects NOD mice from developing diabetes by regulating dendritic cell subsets. Proc Natl Acad Sci U S A 98:13838–13843

    Article  PubMed  CAS  Google Scholar 

  • Nieda M, Okai M, Tazbirkova A, Lin H, Yamaura A, Ide K, Abraham R, Juji T, Macfarlane DJ, Nicol AJ (2004) Therapeutic activation of Valpha24+Vbeta11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity. Blood 103:383–389

    Article  PubMed  CAS  Google Scholar 

  • Oki S, Chiba A, Yamamura T, Miyake S (2004) The clinical implication and molecular mechanism of preferential IL-4 production by modified glycolipid-stimulated NKT cells. J Clin Invest 113:1631–1640

    Article  PubMed  CAS  Google Scholar 

  • Osman Y, Kawamura T, Naito T, Takeda K, Van Kaer L, Okumura K, Abo T (2000) Activation of hepatic NKT cells and subsequent liver injury following administration of alpha-galactosylceramide. Eur J Immunol 30:1919–1928

    Article  PubMed  CAS  Google Scholar 

  • Parekh VV, Wilson MT, Olivares-Villagomez D, Singh AK, Wu L, Wang CR, Joyce S, Van Kaer L (2005) Glycolipid antigen induces long-term natural killer T cell anergy in mice. J Clin Invest 115:2572–2583

    Article  PubMed  CAS  Google Scholar 

  • Porcelli SA, Modlin RL (1999) The CD1 system: antigen-presenting molecules for T cell recognition of lipids and glycolipids. Annu Rev Immunol 17:297–329

    Article  PubMed  CAS  Google Scholar 

  • Reis e Sousa C (2004) Toll-like receptors and dendritic cells: for whom the bug tolls. Semin Immunol 16:27–34

    Article  PubMed  CAS  Google Scholar 

  • Schneider J, Gilbert SC, Hannan CM, Degano P, Prieur E, Sheu EG, Plebanski M, Hill AV (1999) Induction of CD8+ T cells using heterologous prime-boost immunization strategies. Immunol Rev 170:29–38

    Article  PubMed  CAS  Google Scholar 

  • Schulz O, Edwards AD, Schito M, Aliberti J, Manickasingham S, Sher A, Reis e Sousa C (2000) CD40 triggering of heterodimeric IL-12 p70 production by dendritic cells in vivo requires a microbial priming signal. Immunity 13:453–462

    Article  PubMed  CAS  Google Scholar 

  • Seino K, Taniguchi M (2005) Functionally distinct NKT cell subsets and subtypes. J Exp Med 202:1623–1626

    Article  PubMed  CAS  Google Scholar 

  • Silk JD, Hermans IF, Gileadi U, Chong TW, Shepherd D, Salio M, Mathew B, Schmidt RR, Lunt SJ, Williams KJ et al (2004) Utilizing the adjuvant properties of CD1d-dependent NKT cells in T cell-mediated immunotherapy. J Clin Invest 114:1800–1811

    Article  PubMed  CAS  Google Scholar 

  • Smith CL, Dunbar PR, Mirza F, Palmowski MJ, Shepherd D, Gilbert SC, Coulie P, Schneider J, Hoffman E, Hawkins R et al (2005a) Recombinant modified vaccinia Ankara primes functionally activated CTL specific for a melanoma tumor antigen epitope in melanoma patients with a high risk of disease recurrence. Int J Cancer 113:259–266

    Article  PubMed  CAS  Google Scholar 

  • Smith CL, Mirza F, Pasquetto V, Tscharke DC, Palmowski MJ, Dunbar PR, Sette A, Harris AL, Cerundolo V (2005b) Immunodominance of poxviral-specific CTL in a human trial of recombinant-modified vaccinia Ankara. J Immunol 175:8431–8437

    PubMed  CAS  Google Scholar 

  • Smyth MJ, Crowe NY, Pellicci DG, Kyparissoudis K, Kelly JM, Takeda K, Yagita H, Godfrey DI (2002) Sequential production of interferon-gamma by NK1.1(+) T cells and natural killer cells is essential for the antimetastatic effect of alpha-galactosylceramide. Blood 99:1259–1266

    Article  PubMed  CAS  Google Scholar 

  • Solomon M, Sarvetnick N (2004) The pathogenesis of diabetes in the NOD mouse. Adv Immunol 84:239–264

    PubMed  CAS  Google Scholar 

  • Sporri R, Reis e Sousa C (2003) Newly activated T cells promote maturation of bystander dendritic cells but not IL-12 production. J Immunol 171:6406–6413

    PubMed  Google Scholar 

  • Sporri R, Reis e Sousa C (2005) Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4+ T cell populations lacking helper function. Nat Immunol 6:163–170

    Article  PubMed  CAS  Google Scholar 

  • Stober D, Jomantaite I, Schirmbeck R, Reimann J (2003) NKT cells provide help for dendritic cell-dependent priming of MHC class I-restricted CD8+ T cells in vivo. J Immunol 170:2540–2548

    PubMed  CAS  Google Scholar 

  • Terabe M, Matsui S, Park JM, Mamura M, Noben-Trauth N, Donaldson DD, Chen W, Wahl SM, Ledbetter S, Pratt B et al (2003) Transforming growth factor-beta production and myeloid cells are an effector mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance: abrogation prevents tumor recurrence. J Exp Med 198:1741–1752

    Article  PubMed  CAS  Google Scholar 

  • Terabe M, Park JM, Berzofsky JA (2004) Role of IL-13 in regulation of anti-tumor immunity and tumor growth. Cancer Immunol Immunother 53:79–85

    Article  PubMed  CAS  Google Scholar 

  • Thomas SY, Hou R, Boyson JE, Means TK, Hess C, Olson DP, Strominger JL, Brenner MB, Gumperz JE, Wilson SB, Luster AD (2003) CD1d-restricted NKT cells express a chemokine receptor profile indicative of Th1-type inflammatory homing cells. J Immunol 171:2571–2580

    PubMed  CAS  Google Scholar 

  • Van der Vliet HJ, Molling JW, Nishi N, Masterson AJ, Kolgen W, Porcelli SA, van den Eertwegh AJ, von Blomberg BM, Pinedo HM, Giaccone G, Scheper RJ (2003) Polarization of Valpha24+ Vbeta11+ natural killer T cells of healthy volunteers and cancer patients using alpha-galactosylceramide-loaded and environmentally instructed dendritic cells. Cancer Res 63:4101–4106

    PubMed  Google Scholar 

  • Van Kaer L (2005) Alpha-galactosylceramide therapy for autoimmune diseases: prospects and obstacles. Nat Rev Immunol 5:31–42

    Article  PubMed  CAS  Google Scholar 

  • Vincent M, Leslie DS, Gumperz JE, Xiong X, Grant EP, Brenner MB (2002) CD1-dependent dendritic cell instruction. Nat Immunol 3:1163–1168

    Article  PubMed  CAS  Google Scholar 

  • Yu KO, Im JS, Molano A, Dutronc Y, Illarionov PA, Forestier C, Fujiwara N, Arias I, Miyake S, Yamamura T et al (2005) Modulation of CD1d-restricted NKT cell responses by using N-acyl variants of alpha-galactosylceramides. Proc Natl Acad Sci U S A 102:3383–3388

    Article  PubMed  CAS  Google Scholar 

  • Zajonc DM, Cantu C 3rd, Mattner J, Zhou D, Savage PB, Bendelac A, Wilson IA, Teyton L (2005) Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor. Nat Immunol 6:810–818

    Article  PubMed  CAS  Google Scholar 

  • Zeng D, Lewis D, Dejbakhsh-Jones S, Lan F, Garcia-Ojeda M, Sibley R, Strober S (1999) Bone marrow NK1.1(−) and NK1.1(+) T cells reciprocally regulate acute graft versus host disease. J Exp Med 189:1073–1081

    Article  PubMed  CAS  Google Scholar 

  • Zhou D, Mattner J, Cantu C 3rd, Schrantz N, Yin N, Gao Y, Sagiv Y, Hudspeth K, Wu YP, Yamashita T et al (2004) Lysosomal glycosphingolipid recognition by NKT cells. Science 306:1786–1789

    Article  PubMed  CAS  Google Scholar 

  • Zitvogel L, Terme M, Borg C, Trinchieri G (2006) Dendritic cell-NK cell cross-talk: regulation and physiopathology. Curr Top Microbiol Immunol 298:157–174

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cancer Research UK Tumour Immunology Group, The Weatherall Institute of Molecular Medicine, Oxford, OX3 9DS, UK

    V. Cerundolo & M. Salio

Authors
  1. V. Cerundolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Salio
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Brigham and Women’s Hospital, Harvard Medical School, Smith 514 1 Jimmy Fund Way, Boston, MA, 02115, USA

    D. Branch Moody M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Cerundolo, V., Salio, M. (2007). Harnessing NKT Cells for Therapeutic Applications. In: Moody, D.B. (eds) T Cell Activation by CD1 and Lipid Antigens. Current Topics in Microbiology and Immunology, vol 314. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-69511-0_13

Download citation

Publish with us

Policies and ethics

Search

Navigation