A20 Controls Macrophage to Elicit Potent Cytotoxic CD4+ T Cell Response |
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| Authors: | Lifeng Wang Bangxing Hong Xiaoxia Jiang Lindsey Jones Si-Yi Chen Xue F Huang |
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| Institution: | Norris Comprehensive Cancer Center, Department of Molecular Microbiology & Immunology, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America.; University of California San Francisco, United States of America, |
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| 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. |
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