CD26/dipeptidyl peptidase IV differentially regulates the chemotaxis of T cells and monocytes toward RANTES: possible mechanism for the switch from innate to acquired immune response

CD26, a 110 kDa cell surface glycoprotein, exhibits dipeptidyl peptidase IV (DPPIV; EC 3.4.14.5) enzyme activity and plays an important role in T cell co-stimulation, In the present study, the function of CD26/DPFIV in transe ndothelial migration was examined using beta-chemokines as chemoattractants . When soluble recombinant CD26 (sCD26/DPPIV+) was added to the transendoth elial chemotaxis system, chemotactic migration of T cells toward RANTES was significantly enhanced, Addition of sCD26 to 50 ng/ml of RANTES enhanced t he migratory response by a factor of two compared to RANTES alone, whereas mutant soluble CD26 (mCD26), lacking the DPPIV enzyme activity, had no enha ncing effect on RANTES-induced T cell migration, In the process of analyzin g the mechanisms of the enhancement of T cell migration by sCD26, we showed that RANTES was cleaved by sCD26 under physiologic conditions at the preci se site characteristic of its enzyme specificity, However, synthesized RANT ES which lacks two N-terminal amino acids showed a chemotactic activity equ ivalent to full-length RANTES on T cells, Furthermore, addition of sCD26 sh owed enhancement of T cell migration induced by both forms of RANTES. In co ntrast to T cells, the truncated RANTES is inactive in chemotaxis of purifi ed monocytes and supplement of sCD26 but not mCD26 reduced the migratory re sponse of monocytes to RANTES, These results suggest that CD26/DFPIV differ entially regulate the chemotactic response of T cells and monocytes to RANT ES.