Occupancy of dipeptidyl peptidase IV activates an associated tyrosine kinase and triggers an apoptotic signal in human hepatocarcinoma cells.

Dipeptidyl peptidase IV (CD26/DPP-IV) is an ectoenzyme expressed on different cell types. Signaling properties and functional consequences of the CD26 triggering have been elucidated mostly on T cells, where the molecule delivers a costimulatory signal that potentiates T-cell activation through the T-cell receptor. We conducted studies in the human hepatocarcinoma-derived PLC/PRF/5 cell line to examine the signal transduction through CD26 and its functional properties in the absence of other T-cell-specific membrane molecules. Engagement of CD26 in PLC/PRF/5 cells through a specific antibody induces tyrosine phosphorylation of several proteins with maximal intensity 15 minutes after the stimulation. This effect was under the negative regulatory control of CD45 tyrosine phosphatase, in that the addition of orthovanadate clearly enhanced the phosphorylation events. Using in vitro kinase assays with CD26 immunoprecipitates, we observed that a protein or proteins with kinase activity are coprecipitated with the CD26 molecule. In addition, unlike Jurkat T cells, in which CD26 expression exerts a protective effect against apoptosis, in PLC/PRF/5 cells CD26 occupancy delivers a potent apoptotic signal. This effect was also observed in HepG2 cells, thus indicating that it represents a more general phenomenon occurring in different liver neoplastic cell lines.

Apoptosis as a mechanism of peripheral blood mononuclear cell death after measles and varicella-zoster virus infections in children.

Viral infections may induce an acquired form of immunodeficiency, generally lasting a few weeks. In the more severe form, such as HIV infection, the immunodeficiency is permanent. Programmed death of T cells represents one of the mechanisms by which HIV determines the T cell functional impairment, finally resulting in the destruction of T cells. In this study, we evaluated whether an altered regulation of apoptosis was also implicated in the anergy associated with the common measles or varicella-zoster virus (VZV) infections in infancy. A spontaneous apoptosis of peripheral blood mononuclear cells was observed in children who had suffered from these infections as long as 6 mo after the acute disease. Apoptosis was demonstrated through analysis of cellular DNA content, morphologic evidence of cell nuclei shrinkage, and by analysis of DNA degradation. Stimulation of T cells through anti-CD4 MAb increased the number of apoptotic cells with a maximal effect 72 h after the stimulation. Our results suggest that apoptosis may account for the anergy that follows acute viral infections in infancy.