Soluble CD26/Dipeptidyl Peptidase IV Enhances Human Lymphocyte Proliferation In Vitro Independent of Dipeptidyl Peptidase Enzyme Activity and Adenosine Deaminase Binding

Denise Yu, L Slaitini, V Gysbers, A. Riekhoff, Thilo Kahne, H. Knott, Ingrid De Meester, Catherine Abbott, Geoffrey McCaughan, Mark Gorrell

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    44 Citations (Scopus)

    Abstract

    Human CD26 has dipeptidyl peptidase-4 (DPP IV) enzyme activity and binds to adenosine deaminase (ADA). CD26 is costimulatory for lymphocytes and has a circulating soluble form (sCD26). DPP IV enzyme inhibition is a new successful type 2 diabetes therapy. We examined whether the ADA binding and catalytic functions of sCD26 contribute to its effects on T-cell proliferation. Wildtype soluble recombinant human CD26 (srhCD26), an enzyme inactive mutant (srhCD26E-) and an ADA non-binding mutant (srhCD26A-) were co-incubated in in vitro T-cell proliferation assays with peripheral blood mononuclear cells (PBMC) stimulated with phytohaemagglutinin (PHA), muromonab-CD3 or Herpes simplex virus antigen (HSV Ag). Both srhCD26 and srhCD26E- enhanced PHA-induced T-cell proliferation dose-dependently in all six subjects tested. srhCD26 and srhCD26A- had no overall effect on anti-CD3-stimulated PBMC proliferation in four of five subjects. srhCD26, srhCD26E- and srhCD26A- enhanced HSV Ag induced PBMC proliferation in low responders to HSV Ag, but had no effect or inhibited proliferation in HSV-high responders. Thus, effects of soluble human CD26 on human T-cell proliferation are mechanistically independent of both the enzyme activity and the ADA-binding capability of sCD26.

    Original languageEnglish
    Pages (from-to)102-111
    Number of pages10
    JournalScandinavian Journal of Immunology
    Volume73
    Issue number2
    DOIs
    Publication statusPublished - 2011

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