| First Author | van den Brandt J | Year | 2004 |
| Journal | Mol Endocrinol | Volume | 18 |
| Issue | 3 | Pages | 687-95 |
| PubMed ID | 14701943 | Mgi Jnum | J:119838 |
| Mgi Id | MGI:3703367 | Doi | 10.1210/me.2003-0390 |
| Citation | van den Brandt J, et al. (2004) Resistance of single-positive thymocytes to glucocorticoid-induced apoptosis is mediated by CD28 signaling. Mol Endocrinol 18(3):687-95 |
| abstractText | 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-X(L) via a calcium- and phosphatidylinositol 3 kinase-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. |
