Dipeptidyl peptidase IV (CD26): role in T cell activation and autoimmune disease.
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. In the present study, we show by flow cytometry and by enzymatic DP IV assay that myelin basic protein (MBP)-specific, CD4+ T cell clones (TCC) derived from patients with multiple sclerosis (MS) express high levels of DP IV/CD26. The 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 hours after PHA stimulation. The DP IV inhibitors Lys[Z(NO2)]-thiazolidide and Lys[Z(NO2)]-pyrrolidide suppress in a dose-dependent manner DNA synthesis and IFN-gamma, IL-4, and TNF-alpha production of the antigen-stimulated TCC. These data suggest that CD26 plays a role in regulating activation of autoreactive TCC. Further in vivo investigations will clarify, whether the inhibition of the enzymatic activity of DP IV could be a useful tool for therapeutic interventions in MS and/or other autoimmune diseases.
Reinhold
D
D
Department of Internal Medicine, Otto-von-Guericke-University, Magdeburg, Germany.
Hemmer
B
B
Gran
B
B
Steinbrecher
A
A
Brocke
S
S
Kähne
T
T
Wrenger
S
S
Born
I
I
Faust
J
J
Neubert
K
K
Martin
R
R
Ansorge
S
S
D001327:Autoimmune Diseases / Q000201:enzymology* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D004261:DNA Replication / Q000187:drug effects; D018819:Dipeptidyl Peptidase 4 / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000201:enzymology* / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D016056:Immunodominant Epitopes; D008222:Lymphokines; D004676:Myelin Basic Protein; D010835:Phytohemagglutinins; D011759:Pyrrolidines; D015842:Serine Proteinase Inhibitors; D013844:Thiazoles; C110164:lysyl-(Z(nitro))pyrrolidide; C093632:lysyl-(Z(nitro))thiazolidide; D018819:Dipeptidyl Peptidase 4; D008239:Lysine