Inhibitors of dipeptidyl peptidase IV/CD26 suppress activation of human MBP-specific CD4 + T cell clones

Dirk Reinhold, Bernhard Hemmer, Bruno Gran, Ilona Born, Jürgen Faust, Klaus Neubert, Henry F. McFarland, Roland Martin, Siegfried Ansorge

Research output: Contribution to journalArticle

Abstract

The ectoenzyme dipeptidyl peptidase IV (DP IV, EC 3.4.14.5, CD26) has been shown to play a crucial role in T cell activation. Specific inhibitors of DP IV suppress DNA synthesis as well as cytokine production (IL-2, IL-10, IL-12, IFN-γ) of stimulated human and mouse T cells suggesting a potential application of these effectors in transplantations and autoimmune diseases. In the present study, we have examined the expression of DP IV/CD26 on six myelin basic protein (MBP)(87-99)-specific, CD4 + T cell clones (TCC) derived from patients with multiple sclerosis (MS) as well as the biological effects of the two synthetic DP IV inhibitors Lys[Z(NO2)]-thiazolidide and Lys[Z(NO2)]-pyrrolidide on the function of these cells. All TCC expressed high levels of DP IV/CD26, as shown by flow cytometry and by enzymatic DP IV assay. Enzymatic activity of resting TCC was found to be three to fourfold higher than on resting peripheral blood T cells and close to that of T cells 48 h after PHA stimulation. The DP IV inhibitors suppress DNA synthesis and IFN-γ, IL-4, and TNF-α production of the antigen-stimulated TCC. These data suggest that CD26 plays a role in regulation of activation of autoreactive TCC. Further in-vivo investigations, first in experimental models, will clarify, whether the inhibition of the enzymatic activity of DP IV could be a useful tool for therapeutic interventions in MS or other autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)203-209
Number of pages7
JournalJournal of Neuroimmunology
Volume87
Issue number1-2
DOIs
StatePublished - Jul 1 1998
Externally publishedYes

Keywords

  • Autoimmunity
  • CD26
  • Dipeptidyl peptidase IV
  • Inhibitors
  • Multiple sclerosis
  • Myelin basic protein
  • T lymphocyte

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

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    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. Journal of Neuroimmunology, 87(1-2), 203-209. https://doi.org/10.1016/S0165-5728(98)00100-3