help button home button Endocrine Society Molecular Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on December 30, 2003
Molecular Endocrinology, doi:10.1210/me.2003-0390
A more recent version of this article appeared on March 1, 2004
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
18/3/687    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow NURSA Molecule Pages Link
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by van den Brandt, J.
Right arrow Articles by Reichardt, H. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van den Brandt, J.
Right arrow Articles by Reichardt, H. M.

Submitted on October 9, 2003
Accepted on December 19, 2003

Resistance of single-positive thymocytes to glucocorticoid-induced apoptosis is mediated by CD28 signaling

Jens van den Brandt1, Dapeng Wang1, and Holger M. Reichardt1*

1 Institute of Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, 97078 Würzburg, Germany

* To whom correspondence should be addressed. E-mail: holger.reichardt{at}mail.uni-wuerzburg.de.

Glucocorticoids administered in pharmacological doses potently induce apoptosis in immature double-positive thymocytes. In contrast, single-positive thymocytes are completely resistant. We now provide evidence that this difference can be attributed to CD28 signaling. When taken into culture single-positive thymocytes also become sensitive to glucocorticoid-induced apoptosis, which can be prevented by enforced CD28 engagement using a novel type of antibody. This is achieved, at least in part, by transcriptional regulation of apoptosis-related genes such as Bcl-XL via a calcium and PI3K dependent pathway. Accordingly, deficiency of CD28 in genetically engineered mice leads to an increased sensitivity of single-positive thymocytes toward glucocorticoid-induced cell death in vivo. Taken together, we have identified CD28 signaling in the thymus as a key player in determining the differential sensitivity of double-positive and single-positive cells to glucocorticoid-action.
Key words: apoptosis • Bcl-2 family • CD28 • glucocorticoids • thymocytes

NURSA Molecule Pages Link:

Ligands:   Dexamethasone



This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
J. v. d. Brandt, F. Luhder, K. G. McPherson, K. L. de Graaf, D. Tischner, S. Wiehr, T. Herrmann, R. Weissert, R. Gold, and H. M. Reichardt
Enhanced Glucocorticoid Receptor Signaling in T Cells Impacts Thymocyte Apoptosis and Adaptive Immune Responses
Am. J. Pathol., March 1, 2007; 170(3): 1041 - 1053.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
D. V. Delfino, M. Agostini, S. Spinicelli, P. Vito, and C. Riccardi
Decrease of Bcl-xL and augmentation of thymocyte apoptosis in GILZ overexpressing transgenic mice
Blood, December 15, 2004; 104(13): 4134 - 4141.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2003 by The Endocrine Society