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

• Published in: Scandinavian journal of immunology Vol. 73; no. 2; pp. 102 - 111
• Main Authors: Yu, D.M.T, Slaitini, L, Gysbers, V, Riekhoff, A.G.M, Kähne, T, Knott, H.M, De Meester, I, Abbott, C.A, McCaughan, G.W, Gorrell, M.D
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2011
• Subjects: Adenosine Deaminase - metabolism; Adult; Cell Proliferation; Cells, Cultured; Dipeptidyl Peptidase 4 - immunology; Dipeptidyl Peptidase 4 - metabolism; Female; Humans; Indexing in process; Lymphocyte Activation; Lymphocytes - cytology; Lymphocytes - enzymology; Lymphocytes - immunology; Male; Middle Aged; Protein Binding; Solubility; Young Adult
• ISSN: 0300-9475; 1365-3083; 1365-3083
• DOI: 10.1111/j.1365-3083.2010.02488.x

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.