{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:04:16Z","timestamp":1790291056537,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2012,9,1]],"date-time":"2012-09-01T00:00:00Z","timestamp":1346457600000},"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":[[2012,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CD5 activates casein kinase 2 (CK2), a serine\/threonine kinase that constitutively associates with the CK2-binding domain at the end of its cytoplasmic tail. To determine the physiological significance of CD5-dependent CK2 activation in T cells, we generated a knock-in mouse that expresses a CD5 protein containing a microdeletion with selective inability to interact with CK2 (CD5\u0394CK2BD). The levels of CD5 on developing and mature T cell populations from CD5\u0394CK2BD mice and CD5 wild-type (WT) mice were similar. The thymus of CD5\u0394CK2BD mice contained fewer double-positive thymocytes than did that of both CD5WT and CD5 knockout (KO) mice, although the numbers of all other immature and mature T cell populations were unaltered. CD5\u0394CK2BD T cells hypoproliferated and exhibited enhanced activation-induced cell death when stimulated with anti-CD3 or cognate peptide in comparison with CD5WT T cells. We also found that functional CD5-dependent CK2 signaling was necessary for efficient differentiation of naive CD4+ T cells into Th2 and Th17 cells, but not Th1 cells. We previously showed that experimental autoimmune encephalomyelitis (EAE) in CD5KO mice was less severe and delayed in onset than in CD5WT mice. Remarkably, CD5\u0394CK2BD mice recapitulated both EAE severity and disease onset of CD5KO mice. Increasing the immunization dose of myelin oligodendrocyte glycoprotein 35\u201355 peptide, a model that mimics high-dose tolerance, led to decreased severity of EAE in CD5WT mice but not in CD5KO or CD5\u0394CK2BD mice. This property was recapitulated in in vitro restimulation assays. These results demonstrate that CD5\u2013CK2 signaling sets the threshold for T cell responsiveness and is necessary for efficient generation of Th2 and Th17 cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1200065","type":"journal-article","created":{"date-parts":[[2012,8,18]],"date-time":"2012-08-18T05:40:11Z","timestamp":1345268411000},"page":"2918-2930","source":"Crossref","is-referenced-by-count":50,"title":["CD5-Dependent CK2 Activation Pathway Regulates Threshold for T Cell Anergy"],"prefix":"10.1093","volume":"189","author":[{"given":"Christine M","family":"Sestero","sequence":"first","affiliation":[{"name":"Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald J","family":"McGuire","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"De Sarno","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily C","family":"Brantley","sequence":"additional","affiliation":[{"name":"Department of Thoracic\/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Soldevila","sequence":"additional","affiliation":[{"name":"Departamento de Inmunolog\u00eda, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico , 04510 M\u00e9xico City, Distrito Federal,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C","family":"Axtell","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University , Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chander","family":"Raman","sequence":"additional","affiliation":[{"name":"Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham , Birmingham, AL 35294"},{"name":"Department of Microbiology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,9,15]]},"reference":[{"key":"2025032409251822700_r1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1126\/science.7542801","article-title":"A role for CD5 in TCR-mediated signal transduction and thymocyte selection","volume":"269","author":"Tarakhovsky","year":"1995","journal-title":"Science"},{"key":"2025032409251822700_r2","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1126\/science.274.5294.1906","article-title":"CD5-mediated negative regulation of antigen receptor-induced growth signals in B-1 B cells","volume":"274","author":"Bikah","year":"1996","journal-title":"Science"},{"key":"2025032409251822700_r3","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1128\/MCB.19.4.2903","article-title":"CD5 negatively regulates the T-cell antigen receptor signal transduction pathway: involvement of SH2-containing phosphotyrosine phosphatase SHP-1","volume":"19","author":"Perez-Villar","year":"1999","journal-title":"Mol. 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