| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Dipartimento di Medicina Clinica e Sperimentale, Sezione di Farmacologia, Tossicologia e Chemioterapia, Università di Perugia, and IBiT Foundation, Perugia, Italy
CD28 is well characterized as a costimulatory molecule in T cell activation. Recent evidences indicate that TNFR superfamily members, including glucocorticoid-induced TNFR-related protein (GITR), act as costimulatory molecules. In this study, the relationship between GITR and CD28 has been investigated in murine CD8+ T cells. When suboptimal doses of anti-CD3 Ab were used, the absence of GITR lowered CD28-induced activation in these cells whereas the lack of CD28 did not affect the response of CD8+ T cells to GITR costimulus. In fact, costimulation of CD28 in anti-CD3-activated GITR–/– CD8+ T cells resulted in an impaired increase of proliferation, impaired protection from apoptosis, and an impaired rise of activation molecules such as IL-2R, IL-2, and IFN-
. Most notably, CD28-costimulated GITR–/– CD8+ T cells revealed lower NF-
B activation. As a consequence, up-regulation of Bcl-xL, one of the major target proteins of CD28-dependent NF-B activation, was defective in costimulated GITR–/– CD8+ T cells. What contributed to the response to CD28 ligation in CD8+ T cells was the early up-regulation of GITR ligand on the same cells, the effect of which was blocked by the addition of a recombinant GITR-Fc protein. Our results indicate that GITR influences CD8+ T cell response to CD28 costimulation, lowering the threshold of CD8+ T cell activation.
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 a research grant from the Italian Association for Cancer Research (AIRC) in Milan, Italy.
2 S.R. and G.N. equally contributed to this work.
3 Address correspondence and reprint requests to Dr. Carlo Riccardi, Dipartimento di Medicina Clinica e Sperimentale, Sezione di Farmacologia, Università di Perugia, Via del Giochetto, Perugia. E-mail address: riccardi{at}unipg.it
4 Abbreviations used in this paper: TNFRSF, TNFR superfamily; GITR, glucocorticoid-induced TNFR-related protein; GITRL, GITR ligand; MFI, median fluorescence intensity.
This article has been cited by other articles:
|
|
 |
|
  R. W. van Olffen, N. Koning, K. P. J. M. van Gisbergen, F. M. Wensveen, R. M. Hoek, L. Boon, J. Hamann, R. A. W. van Lier, and M. A. Nolte GITR Triggering Induces Expansion of Both Effector and Regulatory CD4+ T Cells In Vivo J. Immunol., June 15, 2009; 182(12): 7490 - 7500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. J. Kraus, J. S. Haring, and G. A. Bishop TNF Receptor-Associated Factor 5 Is Required for Optimal T Cell Expansion and Survival in Response to Infection J. Immunol., December 1, 2008; 181(11): 7800 - 7809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Nishikawa, T. Kato, M. Hirayama, Y. Orito, E. Sato, N. Harada, S. Gnjatic, L. J. Old, and H. Shiku Regulatory T Cell-Resistant CD8+ T Cells Induced by Glucocorticoid-Induced Tumor Necrosis Factor Receptor Signaling Cancer Res., July 15, 2008; 68(14): 5948 - 5954. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Nocentini, S. Cuzzocrea, T. Genovese, R. Bianchini, E. Mazzon, S. Ronchetti, E. Esposito, D. P. Rosanna, P. Bramanti, and C. Riccardi Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related (GITR)-Fc Fusion Protein Inhibits GITR Triggering and Protects from the Inflammatory Response after Spinal Cord Injury Mol. Pharmacol., June 1, 2008; 73(6): 1610 - 1621. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
