Costimulation of human CD28- T cells by 4-1BB ligand.
The T cell surface protein CD28 provides a critical costimulatory signal for T cell activation. With age, humans accumulate increasing numbers of CD28- T cells, and this loss of CD28 expression is exacerbated certain disease states, such as HIV infection, autoimmune conditions or cancer. It is unclear whether CD28- T cells represent terminally differentiated effector cells or whether they remain sensitive to costimulation by CD28-independent pathways. Here, we demonstrate that 4-1 BB ligand can costimulate human CD28- T cells, resulting in cell division, inflammatory cytokine production, increased perforin levels, enhancement of cytolytic effector function, as well as the up-regulation of the anti-apoptotic protein Bcl-X(L). Thus, human CD28- T cells can respond to costimulatory signals and as such become attractive targets for therapeutic intervention, particularly in chronic infectious and inflammatory diseases where large numbers of these cells accumulate.
Bukczynski
Jacob
J
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
Wen
Tao
T
Watts
Tania H
TH
D053330:4-1BB Ligand; D000328:Adult; D000818:Animals; D015703:Antigens, CD; D018106:CD28 Antigens / Q000032:analysis*; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation; D012515:Mast-Cell Sarcoma / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000494:pharmacology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014407:Tumor Cells, Cultured; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects; D051020:bcl-X Protein
D053330:4-1BB Ligand; D015703:Antigens, CD; C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D018106:CD28 Antigens; D016207:Cytokines; D008562:Membrane Glycoproteins; D016853:Muromonab-CD3; D052899:Pore Forming Cytotoxic Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C505714:TNFRSF9 protein, human; C505974:TNFSF9 protein, human; C505715:Tnfrsf9 protein, mouse; C505975:Tnfsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D054353:Perforin