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Conserved region C (CR-C), a promoter proximal cis-regulatory element that is critical to PD-1 expression in vitro, responds to NFATc1, FoxO1, and\/or NF-\u03baB signaling pathways. Here, a CR-C knockout mouse was established to determine its role on PD-1 expression and the corresponding effects on T cell function in vivo. Deletion of CR-C decreased PD-1 expression on CD4 T cells and Ag-specific CD8 T cells during acute and chronic lymphocytic choriomeningitis virus challenges, but did not affect the ability to clear an infection. Following acute lymphocytic choriomeningitis virus infection, memory CD8 T cells in the CR-C knockout mouse were formed in greater numbers, were more functional, and were more effective at responding to a melanoma tumor than wild-type memory cells. These data implicate a critical role for CR-C in governing PD-1 expression, and a subsequent role in guiding CD8 T cell differentiation. The data suggest the possibility that titrating PD-1 expression during CD8 T cell activation could have important ramifications in vaccine development and clinical care.<\/jats:p>","DOI":"10.4049\/jimmunol.1601464","type":"journal-article","created":{"date-parts":[[2016,11,29]],"date-time":"2016-11-29T02:51:02Z","timestamp":1480387862000},"page":"205-217","source":"Crossref","is-referenced-by-count":24,"title":["Conserved Region C Functions To Regulate PD-1 Expression and Subsequent CD8 T Cell Memory"],"prefix":"10.1093","volume":"198","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4494-5033","authenticated-orcid":false,"given":"Alexander P R","family":"Bally","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1941-8282","authenticated-orcid":false,"given":"Joshua T","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin G","family":"Barwick","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D","family":"Evavold","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2432-1840","authenticated-orcid":false,"given":"Jeremy M","family":"Boss","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA 30322"},{"name":"Emory Vaccine Center, Emory University School of Medicine , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,1,1]]},"reference":[{"key":"2025030614575739100_r1","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.immuni.2007.09.006","article-title":"Molecular signature of CD8+ T cell exhaustion during chronic viral infection","volume":"27","author":"Wherry","year":"2007","journal-title":"Immunity"},{"key":"2025030614575739100_r2","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1097\/QAD.0000000000000362","article-title":"Programmed death-1 expression on HIV-1-specific CD8+ T cells is shaped by epitope specificity, T-cell receptor clonotype usage and antigen load","volume":"28","author":"Kl\u00f8verpris","year":"2014","journal-title":"AIDS"},{"key":"2025030614575739100_r3","doi-asserted-by":"crossref","first-page":"S45","DOI":"10.4049\/jimmunol.178.Supp.43.43","article-title":"PD-1 expression on memory CD8 and CD4 T-cell subsets in healthy humans","volume":"178","author":"Jaikumar","year":"2007","journal-title":"J. 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