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

被引:91
作者
Iwata, S
Yamaguchi, N
Munakata, Y
Ikushima, H
Lee, JF
Hosono, O
Schlossman, SF
Morimoto, C [1 ]
机构
[1] Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dept Biol Mol, Boston, MA 02115 USA
[4] Dana Farber Canc Inst, Mol Biol Core Facil, Boston, MA 02115 USA
[5] Univ Tokyo, Inst Med Sci, Dept Clin Immunol, Minato Ku, Tokyo 108, Japan
[6] Univ Tokyo, Inst Med Sci, Ctr AIDS Res, Minato Ku, Tokyo 108, Japan
关键词
beta-chemokine; CD26; dipeptidyl peptidase IV; RANTES; transendothelial migration;
D O I
10.1093/intimm/11.3.417
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 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/DFPIV differentially regulate the chemotactic response of T cells and monocytes to RANTES.
引用
收藏
页码:417 / 426
页数:10
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