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/DPPIV 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 (mCD26), 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 acids 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.
Iwata
S
S
Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Yamaguchi
N
N
Munakata
Y
Y
Ikushima
H
H
Lee
J F
JF
Hosono
O
O
Schlossman
S F
SF
Morimoto
C
C
D000595:Amino Acid Sequence; D018946:Chemokine CCL5 / Q000378:metabolism / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism / Q000494:pharmacology*; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D012995:Solubility; D013601:T-Lymphocytes / Q000187:drug effects*
D018946:Chemokine CCL5; D010446:Peptide Fragments; D018819:Dipeptidyl Peptidase 4