{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:04:51Z","timestamp":1791295491876,"version":"4.1.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T00:00:00Z","timestamp":1375315200000},"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":[[2013,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Human plasmacytoid dendritic cells (pDC) are important modulators of adaptive T cell responses during viral infections. Recently, we found that human pDC produce the serine protease granzyme B (GrB), thereby regulating T cell proliferation in a GrB-dependent manner. In this study, we demonstrate that intrinsic GrB production by pDC is significantly inhibited in vitro and in vivo by clinically used vaccines against viral infections such as tick-borne encephalitis. We show that pDC GrB levels inversely correlate with the proliferative response of coincubated T cells and that GrB suppression by a specific Ab or a GrB substrate inhibitor results in enhanced T cell proliferation, suggesting a predominant role of GrB in pDC-dependent T cell licensing. Functionally, we demonstrate that GrBhigh but not GrBlow pDC transfer GrB to T cells and may degrade the \u03b6-chain of the TCR in a GrB-dependent fashion, thereby providing a possible explanation for the observed T cell suppression by GrB-expressing pDC. Modulation of pDC-derived GrB activity represents a previously unknown mechanism by which both antiviral and vaccine-induced T cell responses may be regulated in vivo. Our results provide novel insights into pDC biology during vaccinations and may contribute to an improvement of prophylactic and therapeutic vaccines.<\/jats:p>","DOI":"10.4049\/jimmunol.1203479","type":"journal-article","created":{"date-parts":[[2013,6,20]],"date-time":"2013-06-20T04:36:02Z","timestamp":1371702962000},"page":"1144-1153","source":"Crossref","is-referenced-by-count":14,"title":["Antiviral Vaccines License T Cell Responses by Suppressing Granzyme B Levels in Human Plasmacytoid Dendritic Cells"],"prefix":"10.1093","volume":"191","author":[{"given":"Dorit","family":"Fabricius","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University Medical Center Ulm , 89075 Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Nu\u00dfbaum","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Ulm , 89075 Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Busch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Ulm , 89075 Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Panitz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Ulm , 89075 Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Mandel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Ulm , 89075 Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Vollmer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Ulm , 89075 Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike-Andrew","family":"Westhoff","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Ulm , 89075 Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Kaltenmeier","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, Ulm University , 89081 Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Lunov","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University , 89081 Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyrylo","family":"Tron","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, Ulm University , 89081 Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G Ulrich","family":"Nienhaus","sequence":"additional","affiliation":[{"name":"Institute of Applied Physics, Institute of Toxicology and Genetics, and Center for Functional Nanostructures, Karlsruhe Institute of Technology , 76131 Karlsruhe,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Jahrsd\u00f6rfer","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, Ulm University , 89081 Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus-Michael","family":"Debatin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Ulm , 89075 Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,8,1]]},"reference":[{"key":"2025032405115980500_r1","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/nri2358","article-title":"Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases","volume":"8","author":"Gilliet","year":"2008","journal-title":"Nat. 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