Analysis of CD26 mediated signal transduction mechanism.

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CD26, a 110 kDa cell surface glycoprotein, exhibits dipeptidyl peptidase IV (DPPIV ; EC3.4.14.5) enzyme activity and plays an important role in T cell costimulation. the function of CD26/dipeptidyl peptidase IV in transendothelial migration was examined using beta-chemokines as chemoattractants. When soluble recombinant CD26 (sCD26/DPPIV^+) was added to the transendothelial chemotaxis system, chemotactic migration of T cells toward RANTES was significantly enhanced. Addition of sCD26 to 50 ng/ml of RANTES enhanced the migratory response by a factor of two compared to RANTES alone, whereas mutant soluble CD26, lacking the DPPIV enzyme activity, had no enhancing effect on RANTES-induced T cell migration. In the process of analyzing the mechanisms of the enhancement of T cell migration by sCD26, we showed that RANTES was cleaved by sCD26 under physiologic conditions at the precise site characteristic of its enzyme specificity. However, synthesized RANTES which lacks two N-terminal amino a … More cids showed a chemotactic activity equivalent to full length RANTES on T cells. Furthermore, addition of sCD26 showed enhancement of T cell migration induced by both forms of RANTES.In contrast to T cells, the truncated RANTES is inactive in chemotaxis of purified monocytes, and supplement of sCD26 but not mCD26 reduced the migratory response of monocytes to RANTES.These results suggest that CD26/DPPIV differentially regulate the chemotactic response of T cells and monocytes to RANTES and furthermore, the finding can partly explain the dominant phenotype at the chronic inflammatory sites in vivo. Stromal cell-derived factor 1alpha (SDF-1alpha) is a chemokine that has been shown to prevent infection of T-tropic HIV strains and is a possible substrate of CD26/DPPIV.We have shown that SDF-1alpha was cleaved at the N-terminal region by CD26/DPPIV and as a result, the inhibitory activity of SDF-1alpha against HIV infection was disappeared. Moreover, the chemotactic activity of SDF-1alpha was also disappeared specifically by DPPIV activity of recombinant soluble CD26. These results suggested that dissemination of T-tropic HIV strains in vivo may be facilitated by CD26/DPPIV via inactivation of functional SDF-1alpha. Less