title: Dipeptidyl peptidase IV (CD26) activity in human alloreactive T cell subsets varies with the stage of differentiation and activation status.
abstract: Dipeptidyl peptidase IV (DPP IV), also known as CD26, is a transmembrane serine aminopeptidase which has an ontogenically related expression on T cells and participates on several immunological functions. CD26 appears to play an important role in alloimmunity during host T cell activation subsequent to alloantigen encounter and is a way by which effector T cells traverse graft endothelial barriers. In order to help to elucidate the role of the CD26 molecule in alloimmune responses, DPP IV activity and CD26 antigenic expression were assessed during the initial phases of completely MHC-disparate human mixed lymphocyte reactions (MLRs) and in several long-term alloreactive T cell clones. Our methods involved the use of a rhodamine-110-conjugated dipeptide substrate specific for DPP IV in two-colour cytofluorographic analysis that allowed stimultaneous lineage marker evaluation. Polyclonal populations of alloreactive CD4 and CD8 T cells contained DPP IV activity at 1 and 10 min of incubation that was variably elevated from resting T cells with the enzyme activity confined to CD26+ cells. T cell clones derived from MLRs were established with IL-2 supplementation and alloantigen restimulation and had reduced CD62L expression with functional specificity to the stimulating MHC. While CD26 expression remained stable, DPP IV activity was variable in the alloreactive T cell clones, with enzyme function in the latter appearing to coincide with the timing of alloantigen restimulation. These studies demonstrate that DPP IV activity varies among phenotypically distinct alloreactive T cell subsets and appears to be altered with the activation status of the effector cells. These findings raise the potential of a role for CD26/DPP IV in the generation of specific alloimmunity. With this methodology, it may be possible to reveal whether specific alterations in the activity of this molecule in T cell populations promote graft acceptance and to determine the molecular requirements for these changes.
authors.affiliation: Department of Pathology, University of Miami School of Medicine, Florida 33101, USA.
authors.forename: P
authors.initials: P
authors.lastname: Ruiz
authors.forename: L
authors.initials: L
authors.lastname: Hao
authors.forename: K
authors.initials: K
authors.lastname: Zucker
authors.forename: N
authors.initials: N
authors.lastname: Zacharievich
authors.forename: A L
authors.initials: AL
authors.lastname: Viciana
authors.forename: M
authors.initials: M
authors.lastname: Shenkin
authors.forename: J
authors.initials: J
authors.lastname: Miller
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002999:Clone Cells / Q000201:enzymology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005434:Flow Cytometry; D006650:Histocompatibility Testing; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D016176:T-Lymphocyte Subsets / Q000201:enzymology*; D013997:Time Factors
chemical_list: D018819:Dipeptidyl Peptidase 4