Mechanisms of CD26/dipeptidyl peptidase IV cytokine-dependent regulation on human activated lymphocytes.

Among the cellular pathways activated by IL-12, we had previously found that both the percentage and intensity of CD26(+)cells in the PHA-stimulated T cells increased when IL-12 was present (independently of its CD4 or CD8 phenotype). Now, we examined the molecular mechanisms of this IL-12-mediated effect. The IL-12 regulation pathway is dependent of de novo protein synthesis and independent of cytokine secretion. Our results show two transcripts for CD26 in PBMC for the first time and no regulation by ILs at this level. Furthermore, secretion of the serum forms of CD26/DPPIV were not affected by IL-12. Interestingly, assays with neutralizing mAbs against TNF-alpha suggest that this cytokine negatively modulates CD26 expression. The fact that translation and probably translocation of CD26 toward the cell surface can be regulated by IL-12 and TNF-alpha reveals new aspects about the control of this T(H1)marker.