Ectopeptidases pp 279-287 | Cite as

CD26/DPIV in Diseases of the Central Nervous System

  • Stefan Brocke
  • Dirk Reinhold
  • Andreas Steinbrecher


The current model for the initiation of T cell-mediated autoimmune inflammatory disease of the central nervous system (CNS) includes peripheral activation of T cells specific for myelin antigens and T helper cell type 1 (Thl) differentiation (Martin et al 1992; Miller and Shevach, 1998). Naive CD4+ T cells develop into either of two major subsets of Th cells that produce distinct sets of cytokines (O’Garra et al 1997). It is widely accepted that Thl cells, critical for cell-mediated immunity by their production of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and lymphotoxin are involved in the immunopathology of organ-specific autoimmune disease (O’Garra et al 1997), including diseases of the CNS (Martin et al 1992). A role as regulators has been suggested for Th2 cells (O’Garra et al 1997) and cells producing transforming growth factor-ß (TGF-ß), recently characterized as Th3 and Tr (regulatory) CD4+ T cells (Weiner 1997). Once primed, autoreactive T cells are able to cross the blood-brain barrier and respond to CNS antigens in situ. Leukocyte accumulation and lesion formation in inflammatory CNS disorders critically depend on antigendriven Thl T cell restimulation in the CNS compartment (Karpus and Ransohoff 1998; Karpus 1999).


Multiple Sclerosis Myelin Basic Protein Lymph Node celIs Experimental Allergic Encephalomyelitis Dipeptidyl Peptidase 
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  1. Annunziato, F., Galli, G., Cosmi, L., Romagnani, P., Manetti, R., Maggi, E., and Romagnani, S., 1998, Molecules associated with human Thl or Th2 cells. Eur. Cytokine Netw.9: 12–16.PubMedGoogle Scholar
  2. De Meester, I., Korom, S., Van Damme, I, and Scharpe, S., 1999, CD26, let it cut or cut it down. Immunol. Today 20: 367–375.PubMedCrossRefGoogle Scholar
  3. Hafler, D.A., Fox, D.A., Manning, M.E., Schlossman, S.F., Reinherz, E.L., and Weiner, H.L., 1985, In vivo activated T lymphocytes in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. N. Engl. J. Med. 312: 1405–1411.PubMedCrossRefGoogle Scholar
  4. Johns, L.D., Flanders, K.C., Ranges, G.E., and Sriram, S., 1991, Successful treatment of experimental allergic encephalomyelitis with transforming growth factor-beta 1. J. Immunol. 147: 1792–1796.PubMedGoogle Scholar
  5. Kähne, T., Lendeckel, U., Wrenger , S., Neubert, K., Ansorge, S., and Reinhold, D., 1999, Dipeptidyl peptidase IV: A cell surface peptidase involved in regulating T cell growth. Int. J.Mol.Med.4: 3–15.PubMedGoogle Scholar
  6. Karpus, W.J., 1999, Chemokine regulation of inflammatory-mediated nervous system diseases. J. Neurovirol. 5: 1–2.PubMedCrossRefGoogle Scholar
  7. Karpus, W.J., and Ransohoff, R.M., 1998, Chemokine regulation of experimental autoimmune encephalomyelitis: temporal and spatial expression patterns govern disease pathogenesis. J. Immunol. 161: 2667–2671.PubMedGoogle Scholar
  8. Kin, Y., Misumi, Y., and Ikehara, Y., 2001, Biosynthesis and characterization of the brainspecific membrane protein DPPX, a dipeptidyl peptidase IV-related protein. J. Biochem.129: 289–295.PubMedCrossRefGoogle Scholar
  9. Khoury, S J., Hancock, W.W., and Weiner, H.L., 1992, Oral tolerance to myelin basic protein and natural recovery from experimental allergic encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor-ß, IL-4, and prostaglandin E in the brain. J. Exp. Med. 176: 1355–1364.PubMedCrossRefGoogle Scholar
  10. Khoury, S.J., Guttmann, C.R., Orav, E.J., Kikinis, R., Jolesz, F.A., and Weiner, H.L., 2000,Changes in activated T cells in the blood correlate with disease activity in multiple sclerosis. Arch. Neurol. 57: 1183–1189.PubMedCrossRefGoogle Scholar
  11. Letterio, J.L. and Roberts, A.B., 1998, Regulation of the immune response by TGF-ß. Annu.Rev. Immunol. 16: 137–161.PubMedCrossRefGoogle Scholar
  12. Martin, R., McFarland, H.F., and McFarlin, D.E., 1992, Immunological aspects of demyelinating diseases. Annu. Rev. Immunol. 10: 153–187.PubMedCrossRefGoogle Scholar
  13. Miller, A., Lider, O., Roberts, A.B., Sporn, M.B., and Weiner, H.L., 1992, Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering. Proc. Natl. Acad. Sci. U.S.A. 89: 421–425.PubMedCrossRefGoogle Scholar
  14. Miller, S.D. and Shevach, E.M., 1998, Immunoregulation of experimental autoimmune encephalomyelitis: editorial overview. Res. Immunol. 149: 753–759.PubMedCrossRefGoogle Scholar
  15. Morimoto, C. and Schlossman, S.F., 1998, The structure and function of CD26 in the T cell immune response. Immunol. Rev. 161: 55–70.PubMedCrossRefGoogle Scholar
  16. O’Garra, A., Steinman, L., and Gijbels, K., 1997, CD4+ T-cell subsets in autoimmunity. Curr.Opin. Immunol. 9: 872–883.CrossRefGoogle Scholar
  17. Racke, M.K., Cannella, B., Albert, P., Sporn, M., Raine, C.S., and McFarlin, D., 1992,Evidence of endogenous regulatory function of transforming growth factor-ß 1 in experimental allergic encephalomyelitis. Int. Immunol. 4: 615–620.PubMedCrossRefGoogle Scholar
  18. Reinhold, D., Bank, U., Buhling, F., Neubert, K., Mattern, T., Ulmer, A.J., Flad, H.D., and Ansorge, S., 1993, Dipeptidyl peptidase IV (CD26) on human lymphocytes. Synthetic inhibitors of and antibodies against dipeptidyl peptidase IV suppress the proliferation of pokeweed mitogen-stimulated peripheral blood mononuclear cells and IL-2 and IL-6 production. Immunobiol. 188: 403–414.CrossRefGoogle Scholar
  19. Reinhold, D., Bank, U., Buhling, F., Lendeckel, U., Faust, J., Neubert, K., and Ansorge, S.,1997a, Inhibitors of dipeptidyl peptidase IV induce secretion of transforming growth factor-ßl in PWM-stimulated PBMC and T cells. Immunology 91: 354–360.PubMedCrossRefGoogle Scholar
  20. Reinhold, D., Bank, U., Buhling, F., Tager, M., Born, I., Faust, J., Neubert, K., and Ansorge,S., 1997b, Inhibitors of dipeptidyl peptidase IV (DP IV, CD26) induces secretion of transforming growth factor-ßl (TGF-ß 1) in stimulated mouse splenocytes and thymocytes.Immunol. Lett. 58: 29–35.PubMedCrossRefGoogle Scholar
  21. Reinhold, D., Hemmer, B., Gran, B., Born, I., Faust, J., Neubert, K., McFarland, H.F., Martin,R., Ansorge, S., 1998, Inhibitors of dipeptidyl peptidase IV/CD26 suppress activation of human MBP-specific CD4+ T cell clones. J. Neuroimmunol. 87: 203–209.PubMedCrossRefGoogle Scholar
  22. Schön, E., Demuth, H.U., Barth, A., and Ansorge, S., 1984, Dipeptidyl peptidase IV of human lymphocytes. Evidence for specific hydrolysis of glycylprolin in T-lymphocytes.Biochem. J. 223: 255–258.PubMedGoogle Scholar
  23. Schön, E., Jahn, S., Kiessig, ST., Demuth, H.U., Neubert, K., Barth, A., Von Baehr, R., and Ansorge, S., 1987, The role of dipeptidyl peptidase IV in human T lymphocyte activation.Inhibitors and antibodies against dipeptidyl peptidase IV suppress lymphocyte proliferation and immunoglobulin synthesis in vitro. Eur. J. Immunol 17: 1821–1826.PubMedCrossRefGoogle Scholar
  24. Sellebjerg, F., Madsen, H.O., Jensen, C.V., Jensen, J., and Garred, P., 2000a, CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis. J. Neuroimmunol 102: 98–106.PubMedCrossRefGoogle Scholar
  25. Sellebjerg, F., Christiansen, M., Jensen, J., and Frederiksen, J.L., 2000b, Immunological effects of oral high-dose methylprednisolone in acute optic neuritis and multiple sclerosis. Eur. J. Neurol. 7:281–289.PubMedCrossRefGoogle Scholar
  26. Steinbrecher, A., Reinhold, D., Quigley, L., Gado, A., Tresser, N., Izikson, L., Born, I., Faust, J., Neubert, K., Martin, R., Ansorge, S., and Brocke, S., 2000, Dipeptidyl peptidase IV in inflammatory CNS disease. Adv. Exp. Med. Biol. 471: 145–153.Google Scholar
  27. Steinbrecher, A., Reinhold, D., Quigley, L., Gado, A., Tresser, N., Izikson, L., Born, I., Faust, J., Neubert, K., Martin, R., Ansorge, S., and Brocke, S., 2001, Targeting dipeptidyl peptidase IV (CD26) suppresses autoimmune encephalomyelitis and up-regulates TGF-ß 1 secretion in vivo. J. Immunol. 166: 2041–2048.PubMedGoogle Scholar
  28. von Bonin, A., Huhn, J., and Fleischer, B., 1998, Dipeptidyl-peptidase IV/CD26 on T cells: analysis of an alternative T-cell activation pathway. Immunol. Rev. 161: 43–53.CrossRefGoogle Scholar
  29. Weiner, H.L., 1997, Oral tolerance for the treatment of autoimmune diseases. Annu. Rev. Med. 48:341–351.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Stefan Brocke
    • 1
  • Dirk Reinhold
    • 2
  • Andreas Steinbrecher
    • 3
  1. 1.Department of PathologyHebrew University Hadassah Medical SchoolJerusalemIsrael
  2. 2.Institute of ImmunologyOtto-von-Guericke UniversityMagdeburgGermany
  3. 3.Department of NeurologyUniversity of RegensburgRegensburgGermany

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