T cell costimulation through CD28 depends on induction of the Bcl-xgamma isoform: analysis of Bcl-xgamma-deficient mice.
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.
Ye
Qunrui
Q
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Press
Barry
B
Kissler
Stephan
S
Yang
Xiao-Feng
XF
Lu
Linrong
L
Bassing
Craig H
CH
Sleckman
Barry P
BP
Jansson
Marianne
M
Panoutsakopoulou
Vily
V
Trimble
Linda A
LA
Alt
Frederick W
FW
Cantor
Harvey
H
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D018106:CD28 Antigens / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002678:Chimera; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D018390:Gene Targeting; D007376:Interleukin-2 / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D020033:Protein Isoforms; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein