International Immunology, Vol. 11, No. 3, 417-426,
March 1999
© 1999 Japanese Society for Immunology
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
1 Division of Tumor Immunology and
2 Molecular Biology Core Facility (MBCF), Dana-Farber Cancer Institute; and Departments of
1 Medicine and
2 Molecular Biology, Harvard Medical School, Boston, MA 02115, USA
3 Department of Clinical Immunology and AIDS Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108, Japan
Correspondence to: C. Morimoto, Division of Tumor Immunology, Dana-Farber Cancer Institute; and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
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 ß-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.
Keywords: ß-chemokine, CD26, dipeptidyl peptidase IV, RANTES, transendothelial migration
The first two authors contributed equally to this work
Transmitting editor: K. Okumura
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