Rescue of thymocytes from glucocorticoid-induced cell death mediated by CD28/CTLA-4 costimulatory interactions with B7-1/B7-2

doi:10.1084/jem.184.5.1631

This Article

	Full Text (PDF)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Wagner, D. H.
	Articles by Newell, M. K.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Wagner, D. H., Jr
	Articles by Newell, M. K.


Social Bookmarking

	What's this?

ARTICLES

Rescue of thymocytes from glucocorticoid-induced cell death mediated by CD28/CTLA-4 costimulatory interactions with B7-1/B7-2

DH Wagner Jr, J Hagman, PS Linsley, W Hodsdon, JH Freed and MK Newell
Division of Basic Immunology, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.

During the differentiation of thymocytes to mature T cells the processes of positive and negative selection result in signals that either protect thymocytes from cell death, or delete, through apoptosis, thymocytes with self-reactive T cell receptors (TCR). Glucocorticoids have been shown to induce thymocyte apoptosis and are produced within the thymic microenvironment. Furthermore, steroid- induced apoptosis of thymocytes has been suggested as a potential mechanism for removal of nonselected thymocytes. In this report, we demonstrate that thymocytes can be rescued from glucocorticoid-induced apoptosis by incubation with cells that express high levels of B7-1 or B7-2. In addition, the ability to be rescued by B7-1 and/or B7-2 can precede expression of the TCR. We demonstrate that CD3(+)-depleted or CD3+/ TCR-beta(+)-doubly depleted thymocytes can be rescued from glucocorticoid-induced apoptosis through the interaction of CD28 or CTLA-4 on thymocytes with cells bearing high levels of B7-1 or B7-2. Furthermore, these transfected cells are major histocompatibility complex (MHC) class II negative and, while they may express MHC class I, there is no preferential rescue of CD8+ thymocytes in the presence of glucocorticoids. Together, these data suggest that the rescue of thymocytes from glucocorticoids can be independent of the TCR. We also demonstrate that, in addition to CD28, CTLA-4 is expressed on thymocytes, suggesting that rescue from glucocorticoid-induced cell death can be mediated by both CD28 and CTLA-4. A CTLA-4Ig fusion protein which binds to both B7-1 and B7-2 was shown to completely block the rescue of thymocytes from glucocorticoid-induced cell death. Therefore, we conclude that interactions between B7-1/B7-2 and CD28/CTLA-4 are sufficient and necessary for rescue of thymocytes from glucocorticoid-induced cell death.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Jeong, S. M., Lee, K. Y., Shin, D., Chung, H., Jeon, S. H., Seong, R. H. (2004). Nitric Oxide Inhibits Glucocorticoid-induced Apoptosis of Thymocytes by Repressing the SRG3 Expression. J. Biol. Chem. 279: 34373-34379 [Abstract] [Full Text]
Ko, M., Jang, J., Ahn, J., Lee, K., Chung, H., Jeon, S. H., Seong, R. H. (2004). T Cell Receptor Signaling Inhibits Glucocorticoid-induced Apoptosis by Repressing the SRG3 Expression via Ras Activation. J. Biol. Chem. 279: 21903-21915 [Abstract] [Full Text]
van den Brandt, J., Wang, D., Reichardt, H. M. (2004). Resistance of Single-Positive Thymocytes to Glucocorticoid-Induced Apoptosis Is Mediated by CD28 Signaling. Mol. Endocrinol. 18: 687-695 [Abstract] [Full Text]
Jamieson, C. A. M., Yamamoto, K. R. (2000). Crosstalk pathway for inhibition of glucocorticoid-induced apoptosis by T cell receptor signaling. Proc. Natl. Acad. Sci. USA 97: 7319-7324 [Abstract] [Full Text]
HACZKU, A., TAKEDA, K., REDAI, I., HAMELMANN, E., CIESLEWICZ, G., JOETHAM, A., LOADER, J., LEE, J.�J., IRVIN, C., GELFAND, E.�W. (1999). Anti-CD86 (B7.2) Treatment Abolishes Allergic Airway Hyperresponsiveness in Mice. Am. J. Respir. Crit. Care Med. 159: 1638-1643 [Abstract] [Full Text]
Battifora, M., Pesce, G., Paolieri, F., Fiorino, N., Giordano, C., Riccio, A. M., Torre, G., Olive, D., Bagnasco, M. (1998). B7.1 Costimulatory Molecule Is Expressed on Thyroid Follicular Cells in Hashimoto's Thyroiditis, But Not in Graves' Disease. J. Clin. Endocrinol. Metab. 83: 4130-4139 [Abstract] [Full Text]
Cilio, C. M., Daws, M. R., Malashicheva, A., Sentman, C. L., Holmberg, D. (1998). Cytotoxic T Lymphocyte Antigen 4�Is Induced in the Thymus upon In Vivo Activation and Its Blockade Prevents Anti-CD3-mediated Depletion of �Thymocytes. J. Exp. Med. 188: 1239-1246 [Abstract] [Full Text]
Zheng, P., Wu, Y., Guo, Y., Lee, C., Liu, Y. (1998). B7-CTLA4 interaction enhances both production of antitumor cytotoxic T lymphocytes and resistance to tumor challenge. Proc. Natl. Acad. Sci. USA 95: 6284-6289 [Abstract] [Full Text]
Chambers, C. A., Cado, D., Truong, T., Allison, J. P. (1997). Thymocyte development is normal in CTLA-4-deficient�mice. Proc. Natl. Acad. Sci. USA 94: 9296-9301 [Abstract] [Full Text]