{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:35:25Z","timestamp":1791300925086,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T00:00:00Z","timestamp":1312156800000},"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":[[2011,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Previous studies have identified the inhibitory role that the programmed death 1 (PD-1) pathway plays during chronic infection. Blockade of this pathway results in rescue of viral-specific CD8 T cells, as well as reduction of viral loads in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). We tested the effect of combining PD ligand 1 (PD-L1) blockade with an agonistic regimen that induces 4-1BB costimulation during chronic LCMV infection. There is a boosting effect in the rescue of LCMV-specific CD8 T cell responses after dual treatment with PD-L1 blockade and 4-1BB agonistic Abs when the amount and timing of 4-1BB costimulation are carefully controlled. When PD-L1\u2013blocking Abs are given together with a single low dose of anti\u20134-1BB agonistic Abs, there is an enhanced and stable expansion of viral-specific CD8 T cells. Conversely, when blocking Abs to PD-L1 are given with a repetitive high dose of anti\u20134-1BB, there is an initial synergistic expansion of viral-specific CD8 T cells by day 7, followed by dramatic apoptosis by day 14. Viral control paralleled CD8 T cell kinetics after dual treatment. By day 7 posttreatment, viral titers were lower in both of the combined regimens (compared with PD-L1 blockade alone). However, whereas the high dose of anti\u20134-1BB plus PD-L1 blockade resulted in rebound of viral titers to original levels, the low dose of anti\u20134-1BB plus PD-L1 blockade resulted in a stable reduction of viral loads. These findings demonstrate the importance of carefully manipulating the balance between activating and inhibitory signals to enhance T cell responses during chronic infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1100077","type":"journal-article","created":{"date-parts":[[2011,7,8]],"date-time":"2011-07-08T23:50:12Z","timestamp":1310169012000},"page":"1634-1642","source":"Crossref","is-referenced-by-count":87,"title":["4-1BB Signaling Synergizes with Programmed Death Ligand 1 Blockade To Augment CD8 T Cell Responses during Chronic Viral Infection"],"prefix":"10.1093","volume":"187","author":[{"given":"Vaiva","family":"Vezys","sequence":"first","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Penaloza-MacMaster","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L","family":"Barber","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Jun","family":"Ha","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogumila","family":"Konieczny","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon J","family":"Freeman","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S","family":"Mittler","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafi","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University , Atlanta, GA 30329"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,8,15]]},"reference":[{"key":"2025032410280308800_r1","doi-asserted-by":"crossref","first-page":"4911","DOI":"10.1128\/JVI.77.8.4911-4927.2003","article-title":"Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment","volume":"77","author":"Wherry","year":"2003","journal-title":"J. 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