2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Sawitzki, B. Articles by Volk, H.-D. Search for Related Content PubMed PubMed Citation Articles by Sawitzki, B. Articles by Volk, H.-D.

IFN- Regulation in Anti-CD4 Antibody–Induced T Cell Unresponsiveness

Birgit Sawitzki^*, Brit Kieselbach^*, Marion Fisser^*, Christian Meisel^*, Katrin Vogt^*, Matthias Gaestel, Manfred Lehmann, Kirsten Risch, Gerald Grütz^* and Hans-Dieter Volk^*

*Department of Medical Immunology, Charité-Campus Mitte, Humboldt-University Berlin, Berlin, Germany; Medical School Hannover, Institute of Biochemistry, Hannover, Germany; and Department of Medical Biochemistry, University of Rostock, Rostock, Germany

Correspondence to B. Sawitzki, Department of Medical Immunology, Charité-Campus Mitte, Humboldt-University Berlin, D-10098 Berlin, Germany. Phone: +49-30-450-524073; Fax: +49-30-450-524932; E-mail: birgit.sawitzki{at}lycos.de

ABSTRACT. The anti-rat CD4 mAb RIB5/2 is very potent in inducing allospecific tolerance in vivo. It is interesting that the unresponsiveness is breakable by exogenous IL-2 applied during the induction phase of tolerance. The molecular mechanisms underlying anti-CD4 antibody–mediated inhibition of allospecific T cell activation and how this is antagonized by exogenous IL-2 were investigated. Anti-CD4 treatment, in vivo and in vitro, completely abrogated IL-2 production by alloreactive T cells. In contrast, anti-CD4–treated alloactivated T cells showed similar IFN- mRNA expression as untreated alloactivated T cells but did not secrete any protein. Thus, the anti-CD4 antibody cannot prevent IFN- mRNA expression but is interfering with posttranscriptional mechanisms that control IFN- production during alloactivation of T cells. Addition of IL-2 but not IL-15 to anti-CD4–treated alloactivated T cells restored IFN- protein production without leading to enhanced IFN- mRNA expression. Further investigations revealed a diminished activation of translation initiation factor eIF2 in anti-CD4–treated T cells, which was restored by exogenous IL-2. As activated eIF2 is essential for the translation of IFN- mRNA, the results may explain the reversibility of anti-CD4–induced unresponsiveness by exogenous IL-2. Furthermore, these results not only shed further light onto the molecular mechanisms of tolerance induction but also reveal the possible weaknesses of anti-CD4 antibody–induced unresponsiveness.

This article has been cited by other articles:

				N. Kim, A. Saudemont, L. Webb, M. Camps, T. Ruckle, E. Hirsch, M. Turner, and F. Colucci The p110delta catalytic isoform of PI3K is a key player in NK-cell development and cytokine secretion Blood, November 1, 2007; 110(9): 3202 - 3208. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673