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Title
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Soluble CD26 / dipeptidyl peptidase IV enhances human lymphocyte proliferation **in vitro** independent of dipeptidyl peptidase enzyme activity and adenosine deaminase binding
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Scandinavian journal of immunology. - Oxford
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Publication
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Oxford
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2011
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ISSN
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0300-9475
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DOI
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10.1111/J.1365-3083.2010.02488.X
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Volume/pages
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73
:2
(2011)
, p. 102-111
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ISI
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000285875800004
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Full text (Publisher's DOI)
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