title: T cell costimulation through CD28 depends on induction of the Bcl-xgamma isoform: analysis of Bcl-xgamma-deficient mice.
abstract: 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.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Qunrui
authors.initials: Q
authors.lastname: Ye
authors.forename: Barry
authors.initials: B
authors.lastname: Press
authors.forename: Stephan
authors.initials: S
authors.lastname: Kissler
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yang
authors.forename: Linrong
authors.initials: L
authors.lastname: Lu
authors.forename: Craig H
authors.initials: CH
authors.lastname: Bassing
authors.forename: Barry P
authors.initials: BP
authors.lastname: Sleckman
authors.forename: Marianne
authors.initials: M
authors.lastname: Jansson
authors.forename: Vily
authors.initials: V
authors.lastname: Panoutsakopoulou
authors.forename: Linda A
authors.initials: LA
authors.lastname: Trimble
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Alt
authors.forename: Harvey
authors.initials: H
authors.lastname: Cantor
mesh_terms: 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
chemical_list: 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