{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:46:39Z","timestamp":1791373599252,"version":"4.3.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Activation of the transcription factor NF-\u03baB is critical for cytokine production and T cell survival after TCR engagement. The effects of persistent NF-\u03baB activity on T cell function and survival are poorly understood. In this study, using a murine model that expresses a constitutively active form of inhibitor of NF-\u03baB kinase \u03b2 (caIKK\u03b2) in a T cell-specific manner, we demonstrate that chronic inhibitor of NF-\u03baB kinase \u03b2 signaling promotes T cell apoptosis, attenuates responsiveness to TCR-mediated stimulation in vitro, and impairs T cell responses to bacterial infection in vivo. caIKK\u03b2 T cells showed increased Fas ligand expression and caspase-8 activation, and blocking Fas\/Fas ligand interactions enhanced cell survival. T cell unresponsiveness was associated with defects in TCR proximal signaling and elevated levels of B lymphocyte-induced maturation protein 1, a transcriptional repressor that promotes T cell exhaustion. caIKK\u03b2 T cells also showed a defect in IL-2 production, and addition of exogenous IL-2 enhanced their survival and proliferation. Conditional deletion of B lymphocyte-induced maturation protein 1 partially rescued the sensitivity of caIKK\u03b2 T cells to TCR triggering. Furthermore, adoptively transferred caIKK\u03b2 T cells showed diminished expansion and increased contraction in response to infection with Listeria monocytogenes expressing a cognate Ag. Despite their functional defects, caIKK\u03b2 T cells readily produced proinflammatory cytokines, and mice developed autoimmunity. In contrast to NF-\u03baB\u2019s critical role in T cell activation and survival, our study demonstrates that persistent IKK\u2013NF-\u03baB signaling is sufficient to impair both T cell function and survival.<\/jats:p>","DOI":"10.4049\/jimmunol.1102429","type":"journal-article","created":{"date-parts":[[2012,7,1]],"date-time":"2012-07-01T00:25:16Z","timestamp":1341102316000},"page":"1209-1219","source":"Crossref","is-referenced-by-count":43,"title":["Chronic Activation of the Kinase IKK\u03b2 Impairs T Cell Function and Survival"],"prefix":"10.1093","volume":"189","author":[{"given":"Sruti","family":"Krishna","sequence":"first","affiliation":[{"name":"Department of Pediatrics-Allergy and Immunology, Duke University Medical Center , Durham, NC 27710"},{"name":"Department of Immunology, Duke University Medical Center , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danli","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pediatrics-Allergy and Immunology, Duke University Medical Center , Durham, NC 27710"},{"name":"School of Laboratory Medicine, Wenzhou Medical College , Wenzhou, Zhejiang Province 325035,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balachandra","family":"Gorentla","sequence":"additional","affiliation":[{"name":"Department of Pediatrics-Allergy and Immunology, Duke University Medical Center , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwook","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics-Allergy and Immunology, Duke University Medical Center , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimin","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Laboratory Medicine, Wenzhou Medical College , Wenzhou, Zhejiang Province 325035,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ping","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics-Allergy and Immunology, Duke University Medical Center , Durham, NC 27710"},{"name":"Department of Immunology, Duke University Medical Center , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,8,1]]},"reference":[{"key":"2025032409214717500_r1","doi-asserted-by":"crossref","first-page":"a000182","DOI":"10.1101\/cshperspect.a000182","article-title":"Roles of the NF-kappaB pathway in lymphocyte development and function","volume":"2","author":"Gerondakis","year":"2010","journal-title":"Cold Spring Harb. 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