{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:35:26Z","timestamp":1791293726663,"version":"4.1.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"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":[[2008,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>After Ag encounter, naive lymphocytes differentiate into populations of memory cells that share a common set of functions including faster response to Ag re-exposure and the ability to self-renew. However, memory lymphocytes in different lymphocyte lineages are functionally and phenotypically diverse. It is not known whether discrete populations of T and B cells use similar transcriptional programs during differentiation into the memory state. We used cross-species genomic analysis to examine the pattern of genes up-regulated during the differentiation of naive lymphocytes into memory cells in multiple populations of human CD4, CD8, and B cell lymphocytes as well as two mouse models of memory development. We identified and validated a signature of genes that was up-regulated in memory cells compared with naive cells in both human and mouse CD8 memory differentiation, suggesting marked evolutionary conservation of this transcriptional program. Surprisingly, this conserved CD8 differentiation signature was also up-regulated during memory differentiation in CD4 and B cell lineages. To validate the biologic significance of this signature, we showed that alterations in this signature of genes could distinguish between functional and exhausted CD8 T cells from a mouse model of chronic viral infection. Finally, we generated genome-wide microarray data from tetramer-sorted human T cells and showed profound differences in this differentiation signature between T cells specific for HIV and those specific for influenza. Thus, our data suggest that in addition to lineage-specific differentiation programs, T and B lymphocytes use a common transcriptional program during memory development that is disrupted in chronic viral infection.<\/jats:p>","DOI":"10.4049\/jimmunol.181.3.1859","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:00:52Z","timestamp":1397847652000},"page":"1859-1868","source":"Crossref","is-referenced-by-count":59,"title":["Identification of an Evolutionarily Conserved Transcriptional Signature of CD8 Memory Differentiation That Is Shared by T and B Cells"],"prefix":"10.1093","volume":"181","author":[{"given":"W Nicholas","family":"Haining","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology"},{"name":"Division of Hematology\/Oncology, Children\u2019s Hospital , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin L","family":"Ebert","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA 02115"},{"name":"Cancer Program, Broad Institute of Harvard and Massachusetts Institute of Technology , Cambridge, MA 02142"},{"name":"Division of Hematology, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aravind","family":"Subrmanian","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of Harvard and Massachusetts Institute of Technology , Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E John","family":"Wherry","sequence":"additional","affiliation":[{"name":"Immunology Program, Wistar Institute , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin","family":"Eichbaum","sequence":"additional","affiliation":[{"name":"Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS , Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Mak","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of Harvard and Massachusetts Institute of Technology , Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Rivoli","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Pretz","sequence":"additional","affiliation":[{"name":"Cancer Program, Broad Institute of Harvard and Massachusetts Institute of Technology , Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Angelosanto","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S","family":"Smutko","sequence":"additional","affiliation":[{"name":"Nugen Technologies , San Carlos, CA 94070"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D","family":"Walker","sequence":"additional","affiliation":[{"name":"Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS , Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M","family":"Kaech","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafi","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University , Atlanta, GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee M","family":"Nadler","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd R","family":"Golub","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology"},{"name":"Division of Hematology\/Oncology, Children\u2019s Hospital , Boston, MA 02115"},{"name":"Cancer Program, Broad Institute of Harvard and Massachusetts Institute of Technology , Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,8,1]]},"reference":[{"key":"2026012806194906500_R1","first-page":"217","article-title":"The role of programming in memory T-cell development","volume-title":"Curr. 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