DIPEPTIDYL PEPTIDASE-IV (CD26) ACTIVITY IN HUMAN ALLOREACTIVE T-CELL SUBSETS VARIES WITH THE STAGE OF DIFFERENTIATION AND ACTIVATION STATUS

Dipeptidyl peptidase IV (DPP IV), also known as CD26, is a transmembra ne serine aminopeptidase which has an ontogenically related expression on T cells and participates in several immunological functions, CD26 appears to play an important role in alloimmunity during host T cell a ctivation subsequent to alloantigen encounter and is a way by which ef fector T cells traverse graft endothelial barriers. In order to help t o elucidate the role of the CD26 molecule in alloimmune responses. DPP IV activity and CD26 antigenic expression were assessed during the in itial phases of completely MHC disparate human mixed lymphocyte reacti ons (MLRs) and in several long-term alloreactive T cell clones. Our me thods involved the use of a rhodamine-110-conjugated dipeptide substra te specific for DPP IV in two-colour cytofluorographic analysis that a llowed stimultaneous lineage marker evaluation. Polyclonal populations of alloreactive CD4 and CD8 T cells contained DPP IV activity at 1 an d 10 min of incubation that was variably elevated from resting T sells with the enzyme activity confined to CD26+ cells. T cell clones deriv ed from MLRs were established with IL-2 supplementation and alloantige n restimulation and had reduced CD26L expression with functional speci ficity to the stimulating MHC. While CD26 expression remained stable. DPP IV activity was variable in the alloreactive T cell clones, with e nzyme function in the latter appearing to coincide with the timing of alloantigen restimulation. These studies demonstrate that DPP IV activ ity varies among phenotypically distinct alloreactive T cell subsets a nd appears to be altered with the activation status of the effector ce lls. These findings raise the potential of a role for CD26 DPP IV in t he 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 de termine the molecular requirements for these changes.