Because of the cytotoxic potential of CD8(+) T cells, maintenance of CD8(+) peripheral tolerance is extremely important. A major peripheral tolerance mechanism is the induction of anergy, a refractory state in which proliferation and IL-2 production are inhibited. We used a TCR transgenic mouse model to investigate the signaling defects in CD8(+) T cells rendered anergic in vivo. In addition to a previously reported alteration in calcium/NFAT signaling, we also found a defect in NF-κB-mediated gene transcription. This was not due to blockade of early NF-κB activation events, including IκB degradation and NF-κB nuclear translocation, as these occurred normally in tolerant T cells. However, we discovered that anergic cells failed to phosphorylate the NF-κB p65 subunit at Ser(311) and also failed to acetylate p65 at Lys(310). Both of these modifications have been implicated as critical for NF-κB transactivation capacity, and thus, our results suggest that defects in key phosphorylation and acetylation events are important for the inhibition of NF-κB activity (and subsequent T cell function) in anergic CD8(+) T cells.
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http://dx.doi.org/10.4049/jimmunol.1100793 | DOI Listing |
J Immunother Cancer
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Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
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Department of Breast Cancer Surgery, Jiangxi Cancer Hospital & Institute, Jiangxi Clinical Research Center for Cancer, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Key Laboratory of Oncology, No. 519 Beijing East Road, Nanchang, Jiangxi, 330029, China.
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View Article and Find Full Text PDFNat Immunol
January 2025
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
BJC Rep
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Laboratory of Hematology-Oncology, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy.
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