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 Google Scholar Google Scholar Articles by Russell, J. Q. Articles by Budd, R. C. Search for Related Content PubMed PubMed Citation Articles by Russell, J. Q. Articles by Budd, R. C.

Anti-CD40L Accelerates Renal Disease and Adenopathy in MRL-lpr Mice in Parallel with Decreased Thymocyte Apoptosis¹

Jennifer Q. Russell^*, Thomas Mooney^*, Philip L. Cohen, Bruce MacPherson, Randolph J. Noelle^§ and Ralph C. Budd^2,*

^* Division of Immunobiology and Department of Pathology, University of Vermont College of Medicine, Burlington, VT 05405; Division of Rheumatology, University of North Carolina School of Medicine, Chapel Hill, NC 27599; and ^§ Department of Microbiology, Dartmouth Medical School, Lebanon, NH 03756

The CD40/CD40L (CD40 ligand) axis regulates several interactions between T cells and B cells. Blocking of CD40 engagement by CD40L inhibits Ig class switch by B cells as well as diminishes T cell response to an immunizing Ag. For these reasons, disruption of CD40/CD40L interactions by anti-CD40L administration or by genetic disruption of CD40L has ameliorated a variety of autoimmune conditions. More recent findings suggest that a direct signal can be transmitted to T cells via their expressed CD40L, which can costimulate proliferation with CD3 or promote germinal center formation. It is therefore possible that treatment with anti-CD40L Ab might produce a different outcome than observed in genetically CD40L-deficient mice. In this regard, we observe that in contrast to the genetic deletion of CD40L in MRL-lpr mice, which diminishes autoimmune disease but has little effect on adenopathy, administration of anti-CD40L to MRL-lpr mice accelerates both of these parameters. This difference appears to result from anti-CD40L actively delivering a signal that inhibits T cell apoptosis in lpr mice. This was confirmed by in vitro studies demonstrating that CD40L cross-linking on lpr thymocytes inhibited apoptosis and surface TCR down-modulation induced by CD3 ligation.