More MS news articles for July 2002

T cell costimulation through CD28 depends on induction of the Bcl-xgamma isoform: analysis of Bcl-xgamma-deficient mice

J Exp Med 2002 Jul 1;196(1):87-95
Ye Q, Press B, Kissler S, Yang XF, Lu L, Bassing CH, Sleckman BP, Jansson M, Panoutsakopoulou V, Trimble LA, Alt FW, Cantor H.
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.

The molecular basis of CD28-dependent costimulation of T cells is poorly understood.

Bcl-xgamma 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-xgamma-deficient (Bcl-xgamma-/-) 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-xgamma largely replaces the requirement for B7-dependent ligation of CD28.

These findings identify the Bcl-xgamma cytosolic protein as an essential downstream link in the CD28-dependent signaling pathway that underlies T cell costimulation.