title: A20 controls macrophage to elicit potent cytotoxic CD4(+) T cell response.
abstract: Emerging evidence indicates that CD4(+) T cells possess cytotoxic potential for tumor eradication and perforin/granzyme-mediated cytotoxicity functions as one of the important mechanisms for CD4(+) T cell-triggered cell killing. However, the critical issue is how the cytotoxic CD4(+) T cells are developed. During the course of our work that aims at promoting immunostimulation of APCs by inhibition of negative regulators, we found that A20-silenced Mф drastically induced granzyme B expression in CD4(+) T cells. As a consequence, the granzyme-highly expressing CD4(+) T cells exhibited a strong cytotoxic activity that restricted tumor development. We found that A20-silenced Mф activated cytotoxic CD4(+) T cells by MHC class-II restricted mechanism and the activation was largely dependent on enhanced production of IFN-γ.
authors.affiliation: Norris Comprehensive Cancer Center, Department of Molecular Microbiology & Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Wang
authors.forename: Bangxing
authors.initials: B
authors.lastname: Hong
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Jiang
authors.forename: Lindsey
authors.initials: L
authors.lastname: Jones
authors.forename: Si-Yi
authors.initials: SY
authors.lastname: Chen
authors.forename: Xue F
authors.initials: XF
authors.lastname: Huang
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology; D053804:Granzymes / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D044767:Ubiquitin-Protein Ligases / Q000276:immunology / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007371:Interferon-gamma; D044767:Ubiquitin-Protein Ligases; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D053804:Granzymes; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse