title: Cutting Edge: Caspase-11 Limits the Response of CD8+ T Cells to Low-Abundance and Low-Affinity Antigens.
abstract: Inflammatory caspases, including caspase-11, are upregulated in CD8(+) T cells after Ag-specific activation, but little is known about their function in T cells. We report that caspase-11-deficient (Casp11(-/-)) T cells proliferated more readily in response to low-affinity and low-abundance ligands both in vitro and in vivo due to an increased ability to signal through the TCR. In addition to increased numbers, Casp11(-/-) T cells had enhanced effector function compared with wild-type cells, including increased production of IL-2 and reduced expression of CD62L. Casp11(-/-) T cells specific for endogenous Ags were more readily deleted than wild-type cells. These data indicate that caspase-11 negatively regulates TCR signaling, possibly through its ability to regulate actin polymerization, and inhibiting its activity could enhance the expansion and function of low-affinity T cells.
authors.affiliation: Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98109 bergst@uw.edu.
authors.forename: Tessa
authors.initials: T
authors.lastname: Bergsbaken
authors.affiliation: Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98109.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bevan
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D020169:Caspases / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D053471:Caspases, Initiator; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D007113:Immunity, Innate; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D019041:L-Selectin / Q000235:genetics / Q000276:immunology; D008089:Listeria monocytogenes / Q000737:chemistry / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D000941:Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D019041:L-Selectin; D010047:Ovalbumin; C101136:Casp4 protein, mouse; D020169:Caspases; D053471:Caspases, Initiator