a20 controls macrophage to elicit potent cytotoxic cd4+ t cell response巨噬细胞表达a20控制引起的细胞毒性cd4 + t细胞反应.pdfVIP

A20 Controls Macrophage to Elicit Potent Cytotoxic CD4+ T Cell Response Lifeng Wang, Bangxing Hong, Xiaoxia Jiang, Lindsey Jones, Si-Yi Chen, Xue F. Huang* Norris Comprehensive Cancer Center, Department of Molecular Microbiology Immunology, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America 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 M 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 M activated cytotoxic CD4+ T cells by MHC class-II restricted mechanism and the activation was largely dependent on enhanced production of IFN-c. Citation: Wang L, Hong B, Jiang X, Jones L, Chen S-Y, et al. (2012) A20 Controls Macrophage to Elicit Potent Cytotoxic CD4+ T Cell Response. PLoS ONE 7(11): e48930. doi:10.1371/journal.pone.0048930 Editor: Russell O. Pieper, University of California San Francisco, United States of America Received July 2, 2012; Accepted October 2, 2012; Published November 7, 2012 Copyright: 2012 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which pe