title: Soluble CD26 / dipeptidyl peptidase IV enhances human lymphocyte proliferation in vitro independent of dipeptidyl peptidase enzyme activity and adenosine deaminase binding.
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.
authors.affiliation: A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Centenary Institute and Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
authors.forename: D M T
authors.initials: DM
authors.lastname: Yu
authors.forename: L
authors.initials: L
authors.lastname: Slaitini
authors.forename: V
authors.initials: V
authors.lastname: Gysbers
authors.forename: A G M
authors.initials: AG
authors.lastname: Riekhoff
authors.forename: T
authors.initials: T
authors.lastname: Kähne
authors.forename: H M
authors.initials: HM
authors.lastname: Knott
authors.forename: I
authors.initials: I
authors.lastname: De Meester
authors.forename: C A
authors.initials: CA
authors.lastname: Abbott
authors.forename: G W
authors.initials: GW
authors.lastname: McCaughan
authors.forename: M D
authors.initials: MD
authors.lastname: Gorrell
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism*; D000328:Adult; D049109:Cell Proliferation; D002478:Cells, Cultured; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D012995:Solubility; D055815:Young Adult
chemical_list: D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase