T Cell Costimulation through CD28 Depends on Induction of the Bcl-xγ Isoform

• Published in: The Journal of experimental medicine Vol. 196; no. 1; pp. 87 - 95
• Main Authors: Ye, Qunrui, Press, Barry, Kissler, Stephan, Yang, Xiao-Feng, Lu, Linrong, Bassing, Craig H., Sleckman, Barry P., Jansson, Marianne, Panoutsakopoulou, Vily, Trimble, Linda A., Alt, Frederick W., Cantor, Harvey
• Format: Journal Article
• Language: English
• Published: 01.07.2002
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20012084

The molecular basis of CD28-dependent costimulation of T cells is poorly understood. Bcl-xγ is a member of the Bcl-x family whose expression is restricted to activated T cells and requires CD28-dependent ligation for full expression. We report that Bcl-xγ–deficient (Bcl-xγ−/−) T cells display defective proliferative and cytokine responses to CD28-dependent costimulatory signals, impaired memory responses to proteolipid protein peptide (PLP), and do not develop PLP-induced experimental autoimmune encephalomyelitis (EAE). In contrast, enforced expression of Bcl-xγ largely replaces the requirement for B7-dependent ligation of CD28. These findings identify the Bcl-xγ cytosolic protein as an essential downstream link in the CD28-dependent signaling pathway that underlies T cell costimulation.