Cytofluorographic evidence that thymocyte dipeptidyl peptidase IV (CD26) activity is altered with stage of ontogeny and apoptotic status

Abstract

CD26 is a multifunctional molecule implied to have a variety of roles in the immune response including its activity as a membrane exopeptidase (Dipeptidyl peptidase IV) which cleaves several protein molecules. In order to further define the expression and functional activity of CD26 in the developing thymus, we utilized a nondisruptive, cytofluorogenic assay which allowed simultaneous measurement of DPP IV activity with a fluorochrome‐conjugated peptide substrate and surface staining of the T lymphocyte lineage antigens CD4 and CD8. Neonatal and adult murine thymi were examined using the three‐color assay and significant differences in DPP IV activity were found among the thymocyte subsets defined by their CD4/CD8 phenotype. Single‐positive cells bore higher activity than CD4−/CD8− cells and neonates had higher activity than adults. Thymocytes with characteristics consistent with apoptotic cells expressed higher DPP IV activity. Thus, DPP IV appears to be upregulated both as thymocytes mature and among thymocytes which are undergoing programmed cell death. These results suggest that CD26 is ontogenically controlled during T cell maturation and may play a role in thymic deletion of emerging clones. © 1996 Wiley‐Liss, Inc.

Inhibition of dipeptidyl peptidase IV by fluoroolefin-containingN-peptidyl-O-hydroxylamine peptidomimetics

“…DPP IV, known to be localized on the surface of T cells with adenosine deaminase, seems to form a complex with adenosine deaminase that is involved in an important immunoregulatory mechanism involving T-cell proliferation (24,25). DPP IV appears to be not only up-regulated among proliferating thymocytes but also by those undergoing programmed cell death (26). The involvement of CD26 in HIV infection has been the subject of investigation for some time, with the initial report (27) that CD26 was a cofactor facilitating HIV entry in CD4 ϩ cells refuted (28)(29)(30).…”

CD26/DPPIV inhibition alters the expression of immune response-related genes in the thymi of NOD mice

“…The migration of developing thymocytes within the thymus is crucial for T cell 345 repertoire selection and requires complex interactions between thymocytes and the 346 surrounding microenvironment (Ruiz et al, 1996). It is well known that chemokines are 347 key elements in intrathymic organization and the migration of thymocytes during their gene expression levels of Ccr7 and Ccl19 were also up-regulated in treated NOD mice, 367 but the differences were not statistically significant.…”