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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0804336v1 183/6/3616    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Liu, Z. Articles by Sundqvist, K.-G. PubMed PubMed Citation Articles by Liu, Z. Articles by Sundqvist, K.-G.

A CD26-Controlled Cell Surface Cascade for Regulation of T Cell Motility and Chemokine Signals¹

Zhiwen Liu^*, Marta Christensson^*, Anna Forslöw^*, Ingrid De Meester and Karl-Gösta Sundqvist^2,*

^* Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital, Huddinge, Stockholm, Sweden; and Department of Pharmaceutical Sciences, Laboratory of Medical Biochemistry, University of Antwerp, Antwerp, Belgium

Chemokines are key regulators of cell trafficking, and dipeptidyl peptidase IV/CD26 (CD26) inactivates chemokines. Here we show that the CD26-processed chemokines SDF1/CXCL12 and RANTES/CCL5, in contrast to a control chemokine not processed by CD26, are potent inducers of cell surface expression of thrombospondin-1 (TSP-1) in T lymphocytes through a CD26-controlled mechanism and that TSP-1 stimulates expression of lipoprotein receptor related protein/CD91. Accordingly, intact TSP-1 and a peptide mimetic of a sequence in TSP-1 were sufficient to stimulate CD91 expression. The chemokine-induced expression of TSP-1 and CD91 was mimicked by inhibitors of CD26 and CXCL12 and CCL5 as well as inhibitors of CD26 stimulated polarized cytoplasmic spreading and migration through TSP-1. Silencing of CD26 using small interfering RNA or Ab-induced modulation of CD26 also increased TSP-1 expression and enhanced cytoplasmic spreading and T cell migration markedly. These results indicate that CD26 is an endogenous inhibitor of T cell motility through inhibition of TSP-1 expression and that chemokines stimulate cell polarity and migration through abrogation of the CD26-dependent inhibition. This suggests that T cell motility is regulated by a cascade of interacting cell surface molecules.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Swedish Research Council Project 56X-20347.

² Address correspondence and reprint requests to Dr. Karl-Gösta Sundqvist, Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital, Huddinge, Stockholm, Sweden. E-mail address: Karl.Sundqvist{at}karolinska.se

³ Abbreviations used in this paper: TSP-1, thrombospondin-1; CD26, dipeptidyl peptidase IV/CD26; CRT, calreticulin; siRNA, small interfering RNA; 4N1K, KRFYVVMWKK; Sc4N1K, KVFRWKYVMK (scrambled 4N1K).