HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bulwin, G.-C. Articles by Utku, N. Search for Related Content PubMed PubMed Citation Articles by Bulwin, G.-C. Articles by Utku, N.

TIRC7 Inhibits T Cell Proliferation by Modulation of CTLA-4 Expression

Grit-Carsta Bulwin^*,, Thomas Heinemann, Volker Bugge^*, Michael Winter^*, Anke Lohan, Mirko Schlawinsky, Anke Schulze^*, Stephanie Wälter, Robert Sabat^*, Ralf Schülein, Burkhard Wiesner, Rüdiger W. Veh^¶, Jürgen Löhler^||, Richard S. Blumberg^#, Hans-Dieter Volk^* and Nalân Utku^1,*,

^* Institut für Medizinische Immunologie, Campus Charité Mitte, Humboldt-Universität zu Berlin, Berlin, Germany; GenPat77 Pharmacogenetics, Berlin, Germany; Kekulé-Institut für Organische Chemie und Biochemie der Universität Bonn, Bonn, Germany; Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany; ^¶ Anatomisches Institut, Campus Mitte, Humboldt-Universität zu Berlin, Berlin, Germany; ^|| Molecular Pathology Group, Heinrich-Pette-Institute, Hamburg, Germany; and ^# Division of Gastroenterology, Brigham and Women’s Hospital, Boston, MA 02115

Ab targeting of TIRC7 has been shown previously to inhibit T cell proliferation and Th1 lymphocyte-associated cytokine production. In this study, we demonstrate that Ab targeting of TIRC7 induces early cell surface expression of CTLA-4. The majority of stimulated CD4⁺ and CD8⁺ human T cells coexpress CTLA-4 and TIRC7. Similar to CTLA-4, TIRC7 rapidly accumulates at the site of Ag adhesion upon T cell activation. TIRC7 seems to colocalize with CTLA-4 in human T cells, and both molecules are associated with clathrin-coated vesicles, indicating they share intracellular transport systems. Moreover, Ab targeting of TIRC7 results in an early activation of CTLA-4 transcription. The inhibition of cell proliferation mediated by TIRC7 is dependent on CTLA-4 expression because the TIRC7-mediated inhibitory effects on cell proliferation and cytokine expression are abolished by Ab blockade of CTLA-4. Splenocytes obtained from CTLA-4-deficient mice are not responsive to TIRC7 Ab targeting. Thus, TIRC7 acts as an upstream regulatory molecule of CTLA-4 expression.

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 Address correspondence and reprint requests to Dr. Nalân Utku, Humboldt University of Berlin, Schumannstrasse 20/21, D-10115 Berlin, Germany. E-mail address: nalan.utku{at}charite.de

This article has been cited by other articles:

				F Sellebjerg, P Datta, J Larsen, K Rieneck, I Alsing, A Oturai, A Svejgaard, P Soelberg Sorensen, and L. Ryder Gene expression analysis of interferon-{beta} treatment in multiple sclerosis Multiple Sclerosis, June 1, 2008; 14(5): 615 - 621. [Abstract] [PDF]