{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T09:54:17Z","timestamp":1780566857514,"version":"3.54.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"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":[[2013,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tumor-targeted vaccines represent a strategy to enhance the graft-versus-leukemia effect after allogeneic blood and marrow transplantation (BMT). We have previously shown that graft-versus-host disease (GVHD) can negatively impact quantitative responses to vaccines. Using a minor histocompatibility Ag\u2013mismatched BMT (B6\u2192B6 \u00d7 C3H.SW) followed by adoptive transfer of HY-specific T cells and HY-expressing dendritic cells, we assessed whether GVHD induced by donor lymphocyte infusion (DLI) affects the persistence, proliferation, and survival of vaccine-responding, nonalloantigen reactive T cells. Both CD8+ and CD4+ HY-specific T cells undergo less vaccine-driven proliferation in allogeneic recipients with GVHD. Although vaccine-responding CD8+ T cells show decreased IFN-\u03b3 and CD107a production, CD4+ T cells exhibit increased programmed death 1 and T cell Ig mucin-like domain 3 expression. In addition, the degree of apoptosis in vaccine-responding CD8+ T cells was higher in the presence of GVHD, but there was no difference in CD4+ T cell apoptosis. Using Fas ligand\u2013deficient or TRAIL-deficient DLI had no impact on apoptosis of HY-specific T cells. However, perforin-deficient alloreactive DLI induced significantly less apoptosis of vaccine-responding CD8+ T cells and resulted in enhanced tumor protection. Thus, diminished vaccine responses during GVHD result from impaired proliferation of CD8+ and CD4+ T cells responding to vaccination, with an additional contribution from perforin-mediated CD8+ T cell apoptosis. These results provide important insights toward optimizing vaccine responses after allogeneic BMT.<\/jats:p>","DOI":"10.4049\/jimmunol.1200391","type":"journal-article","created":{"date-parts":[[2012,12,29]],"date-time":"2012-12-29T04:54:08Z","timestamp":1356756848000},"page":"1351-1359","source":"Crossref","is-referenced-by-count":14,"title":["Graft-versus-Host Disease Impairs Vaccine Responses through Decreased CD4+ and CD8+ T Cell Proliferation and Increased Perforin-Mediated CD8+ T Cell Apoptosis"],"prefix":"10.1093","volume":"190","author":[{"given":"Christian M","family":"Capitini","sequence":"first","affiliation":[{"name":"Blood and Marrow Transplant Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"},{"name":"Department of Pediatrics, University of Wisconsin Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health , Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole M","family":"Nasholm","sequence":"additional","affiliation":[{"name":"Blood and Marrow Transplant Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brynn B","family":"Duncan","sequence":"additional","affiliation":[{"name":"Blood and Marrow Transplant Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Guimond","sequence":"additional","affiliation":[{"name":"University of Montreal, Maisonneuve-Rosemont Hospital , Montreal, Quebec, H1T 2M4","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry J","family":"Fry","sequence":"additional","affiliation":[{"name":"Blood and Marrow Transplant Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,2,1]]},"reference":[{"issue":"1","key":"2025032406274713400_r1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.bbmt.2005.10.015","article-title":"Immune reconstitution: from stem cells to lymphocytes","volume":"12","author":"Crooks","year":"2006","journal-title":"Biol. 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