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Mini Review: Immune Response to Myelin-Derived Sulfatide and CNS-Demyelination

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Abstract

Here we briefly review our understanding of the immune response to myelin-derived glycolipids during an inflammatory autoimmune response in the central nervous system (CNS). We focus primarily on the recognition of the self-glycolipid sulfatide by a distinct population of non-invariant NK T cells. The results of studies we have obtained so far in investigating the presentation of sulfatide by CNS-resident cells including microglia and their interactions with T cells indicate that this pathway might be successfully targeted for the treatment of autoimmune demyelination in multiple sclerosis.

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References

  1. Uhlig H, Dernick R (1989) Monoclonal autoantibodies derived from multiple sclerosis patients and control persons and their reactivities with antigens of the central nervous system. Autoimmunity 5:87–99

    PubMed  CAS  Google Scholar 

  2. Stevens A, Weller M, Wietholter H (1992) CSF and serum ganglioside antibody patterns in MS. Acta Neurol Scand 86:485–489

    Article  PubMed  CAS  Google Scholar 

  3. Bansal AS, Abdul-Karim B, Malik RA, Goulding P, Pumphrey RS, Boulton AJ, Holt PL, Wilson PB (1994) IgM ganglioside GM1 antibodies in patients with autoimmune disease or neuropathy, and controls. J Clin Pathol 47:300–302

    PubMed  CAS  Google Scholar 

  4. Endo T, Deborah D, Scott S, Scott ST, Samar KK, Donald MM (1984) Antibodies to glycosphingolipids in patients with multiple sclerosis and SLE. J Immunol 132:1793–1797

    PubMed  CAS  Google Scholar 

  5. Ilvas AA, Chen ZW, Cook SD (2003) Antibodies to sulfatide in cerebrospinal fluid of patients with multiple sclerosis. J Neuroimmunol 139:76–80

    Article  CAS  Google Scholar 

  6. Steinman L (1996) Multiple sclerosis: a coordinated immunological attack against myelin in the central nervous system. Cell 85:299–302

    Article  PubMed  CAS  Google Scholar 

  7. Prat A, Antel J (2005) Pathogenesis of multiple sclerosis. Curr Opin Neurol 18:225–230

    Article  PubMed  CAS  Google Scholar 

  8. Sospedra M, Martin R (2005) Immunology of multiple sclerosis*. Annu Rev Immunol 23:683–747

    Article  PubMed  CAS  Google Scholar 

  9. Paterson PY (1980) Autoimmune diseases of myelin. Prog Clin Biol Res 49:19–36

    PubMed  CAS  Google Scholar 

  10. Sakaguchi S (2000) Regulatory T cells: key controllers of immunologic self-tolerance. Cell 101:455–458

    Article  PubMed  CAS  Google Scholar 

  11. Jahng AW, Maricic I, Pedersen B, Burdin N, Naidenko O, Kronenberg M, Koezuka Y, Kumar V (2001) Activation of natural killer T cells potentiates or prevents experimental autoimmune encephalomyelitis. J Exp Med 194:1789–1799

    Article  PubMed  CAS  Google Scholar 

  12. 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 

  13. Kumar V (2004) Homeostatic control of immunity by TCR peptide-specific Tregs. J Clin Invest 114:1222–1226

    Article  PubMed  CAS  Google Scholar 

  14. Sela BA, Konat G, Offner H (1982) Elevated ganglioside concentration in serum and peripheral blood lymphocytes from multiple sclerosis patients in remission. J Neurol Sci 54:143–148

    Article  PubMed  CAS  Google Scholar 

  15. Lubetzki C, Thuillier Y, Galli A, Lyon-Caen O, Lhermitte F, Zalc B (1989) Galactosylceramide: a reliable serum index of demyelination in multiple sclerosis. Ann Neurol 26:407–409

    Article  PubMed  CAS  Google Scholar 

  16. Kanter JL, Narayana S, Ho PP, Catz I, Warren KG, Sobel RA, Steinman L, Robinson WH (2006) Lipid microarrays identify key mediators of autoimmune brain inflammation. Nat Med 12:138–143

    Article  PubMed  CAS  Google Scholar 

  17. Shamshiev A, Donda A, Carena I, Mori L, Kappos L, De Libero G (1999) Self glycolipids as T-cell autoantigens. Eur J Immunol 29:1667–1675

    Article  PubMed  CAS  Google Scholar 

  18. Shamshiev A, Donda A, Prigozy TI, Mori L, Chigorno V, Benedict CA, Kappos L, Sonnino S, Kronenberg M, De Libero G (2000) The alphabeta T cell response to self-glycolipids shows a novel mechanism of CD1b loading and a requirement for complex oligosaccharides. Immunity 13:255–264

    Article  PubMed  CAS  Google Scholar 

  19. Battistini L, Fischer FR, Raine CS, Brosnan CF (1996) CD1b is expressed in multiple sclerosis lesions. J Neuroimmunol 67:145–151

    PubMed  CAS  Google Scholar 

  20. 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 

  21. Brigl M, Brenner MB (2004) CD1: antigen presentation and T cell function. Annu Rev Immunol 22:817–890

    Article  PubMed  CAS  Google Scholar 

  22. Moody DB, Zajonc DM, Wilson IA (2005) Anatomy of CD1-lipid antigen complexes. Nat Rev Immunol 5:387–399

    Article  PubMed  CAS  Google Scholar 

  23. Bendelac A, Rivera MN, Park SH, Roark JH (1997) Mouse CD1-specific NK1 T cells: development, specificity, and function. Annu Rev Immunol 15:535–562

    Article  PubMed  CAS  Google Scholar 

  24. Mattner J, Debord KL, Ismail N, Goff RD, Cantu C III, Zhou D, Saint-Mezard P, Wang V, Gao Y, Yin N, Hoebe K, Schneewind O, Walker D, Beutler B, Teyton L, Savage PB, Bendelac A (2005) Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434:525–529

    Article  PubMed  CAS  Google Scholar 

  25. Zajonc DM, Maricic I, Wu D, Halder R, Roy K, Wong CH, Kumar V, Wilson IA (2005) Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity. J Exp Med 202:1517–1526

    Article  PubMed  CAS  Google Scholar 

  26. Matsuda JL, Naidenko OV, Gapin L, Nakayama T, Taniguchi M, Wang CR, Koezuka Y, Kronenberg M (2000) Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers. J Exp Med 192:741–754

    Article  PubMed  CAS  Google Scholar 

  27. Illes Z, Kondo T, Newcombe J, Oka N, Tabira T, Yamamura T (2000) Differential expression of NK T cell V alpha 24J alpha Q invariant TCR chain in the lesions of multiple sclerosis and chronic inflammatory demyelinating polyneuropathy. J Immunol 164:4375–4381

    PubMed  CAS  Google Scholar 

  28. Becher B, Prat A, Antel JP (2000) Brain-immune connection: immuno-regulatory properties of CNS-resident cells. Glia 29:293–304

    Article  PubMed  CAS  Google Scholar 

  29. Aloisi F (2001) Immune function of microglia. Glia 36:165–179

    Article  PubMed  CAS  Google Scholar 

  30. Carson MJ (2002) Microglia as liaisons between the immune and central nervous systems: functional implications for multiple sclerosis. Glia 40:218–231

    Article  PubMed  Google Scholar 

  31. Hickey WF, Kimura H (1988) Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 239:290–292

    Article  PubMed  CAS  Google Scholar 

  32. Byram SC, Carson MJ, DeBoy CA, Serpe CJ, Sanders VM, Jones KJ (2004) CD4-positive T cell-mediated neuroprotection requires dual compartment antigen presentation. J Neurosci 24:4333–4339

    Article  PubMed  CAS  Google Scholar 

  33. Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318

    Article  PubMed  CAS  Google Scholar 

  34. Sedgwick JD, Schwender S, Gregersen R, Dorries R, ter Meulen V (1993) Resident macrophages (ramified microglia) of the adult brown Norway rat central nervous system are constitutively major histocompatibility complex class II positive. J Exp Med 177:1145–1152

    Article  PubMed  CAS  Google Scholar 

  35. Swanberg M, Lidman O, Padyukov L, Eriksson P, Akesson E, Jagodic M, Lobell A, Khademi M, Borjesson O, Lindgren CM, Lundman P, Brookes AJ, Kere J, Luthman H, Alfredsson L, Hillert J, Klareskog L, Hamsten A, Piehl F, Olsson T (2005) MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction. Nat Genet 37:486–494

    Article  PubMed  CAS  Google Scholar 

  36. Youssef S, Stuve O, Patarroyo JC, Ruiz PJ, Radosevich JL, Hur EM, Bravo M, Mitchell DJ, Sobel RA, Steinman L, Zamvil SS (2002) The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 420:78–84

    Article  PubMed  CAS  Google Scholar 

  37. Lovett-Racke AE, Hussain RZ, Northrop S, Choy J, Rocchini A, Matthes L, Chavis JA, Diab A, Drew PD, Racke MK (2004) Peroxisome proliferator-activated receptor alpha agonists as therapy for autoimmune disease. J Immunol 172:5790–5798

    PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by grants from the National Institutes of Health (VK) and from the Multiple Sclerosis National Research Institute (VK). Authors would like to thank our lab colleagues, Drs. Randle Ware and Trevor Smith for a critical reading of the manuscript.

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Authors and Affiliations

  1. Laboratory of Autoimmunity, Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA , 92121, USA

    Ramesh C. Halder, A. Jahng, I. Maricic & Vipin Kumar

Authors
  1. Ramesh C. Halder
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  2. A. Jahng
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  3. I. Maricic
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  4. Vipin Kumar
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Corresponding author

Correspondence to Vipin Kumar.

Additional information

Special issue of the Journal dedicated to Drs. Anthony T. Campagnoni and Celia W. Campagnoni.

It is a privilege to contribute an article for this special occasion. It was highly rewarding for me to participate in the Journal Club meetings at UCLA initiated by Tony in which experts in Neurochemistry, Neurosciences and Immunology would discuss and learn from each other with passion. I personally enjoyed and benefited both from these meetings and especially from the get-togethers at their lovely home overlooking the Santa Monica hills. I will always treasure my association and friendship with Tony and Celia.

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Halder, R.C., Jahng, A., Maricic, I. et al. Mini Review: Immune Response to Myelin-Derived Sulfatide and CNS-Demyelination. Neurochem Res 32, 257–262 (2007). https://doi.org/10.1007/s11064-006-9145-4

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  • DOI: https://doi.org/10.1007/s11064-006-9145-4

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