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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adoptive Transfer
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Animals
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Apoptosis / immunology
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Autoimmunity / immunology
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CD28 Antigens / metabolism*
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CD3 Complex / metabolism
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Cell Cycle / drug effects
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Cell Cycle / immunology
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Cell Division / drug effects
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Cell Division / immunology
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Cells, Cultured
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Chimera
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Gene Expression Regulation / immunology*
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Gene Targeting
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Interleukin-2 / pharmacology
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Mice
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Mice, Inbred Strains
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Mice, Transgenic
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Protein Isoforms / deficiency
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Proto-Oncogene Proteins c-bcl-2 / deficiency
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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bcl-X Protein
Substances
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Bcl2l1 protein, mouse
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CD28 Antigens
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CD3 Complex
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Interleukin-2
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Protein Isoforms
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Proto-Oncogene Proteins c-bcl-2
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bcl-X Protein