{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:02:02Z","timestamp":1791190922596,"version":"4.1.0"},"reference-count":47,"publisher":"The Royal Society","issue":"1395","license":[{"start":{"date-parts":[[2000,3,29]],"date-time":"2000-03-29T00:00:00Z","timestamp":954288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Phil. Trans. R. Soc. Lond. B"],"published-print":{"date-parts":[[2000,3,29]]},"abstract":"<jats:p>Following acute lymphocytic choriomeningitis virus (LCMV) infection, there is a potent antiviral CD8 T\u2013cell response that eliminates the infection. This initial CD8 T\u2013cell response is followed by a period of memory during which elevated numbers of virus\u2013specific CD8 T cells remain in the mouse. CD4 T cells are also activated after LCMV infection, but relatively less is known about the magnitude and duration of the CD4 response. In this study, we used intracellular staining for interferon\u2013\u03b3 to measure both CD4 and CD8 responses in the same mice at the single cell level. After LCMV infection, there was an increase in the number of activated CD4 T cells and an associated increase in the number of virus\u2013specific CD4 T cells. At the peak of this expansion phase, the frequency of virus\u2013specific CD4 T cells was 1 in 20 (0.5\u20131.0 \u00d7 106 per spleen). Like the CD8 response, long\u2013term CD4 memory could be found up to a year after the infection with frequencies of approximately 1 in 260 (0.5\u20131.5 \u00d7 105 per spleen). However, the magnitude of virus\u2013specific CD8 T cells was greater than virus\u2013specific CD4 T cells during all phases of the immune response (expansion, death, and memory). At day 8, there were 20\u2013 to 35\u2013fold more virusspecific CD8 Tcells than CD4 Tcells. This initial difference in cell number lasted into the memory phase as there remained a ten\u2013 to 20\u2013fold difference in the CD8 and CD4 responses. These results highlight the importance of the expansion phase in determining the size of the memory T\u2013cell pool. In addition to the difference in the magnitude, the activation requirements of CD8 and CD4 T\u2013cell responses were different: CD8 T responses were not affected by blockade of CD40\u2013 CD40 ligand interaction whereas CD4 responses were reduced 90%. So while there is long\u2013term memory in both the CD8 and CD4 compartments, the rules regulating the activation of CD8 and CD4 T cells and the overall magnitude of the responses are different.<\/jats:p>","DOI":"10.1098\/rstb.2000.0577","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T19:55:43Z","timestamp":1027713343000},"page":"373-379","source":"Crossref","is-referenced-by-count":46,"title":["Antiviral CD4 and CD8 T\u2013cell memory: differences in the size of the response and activation requirements"],"prefix":"10.1098","volume":"355","author":[{"given":"Jason K.","family":"Whitmire","sequence":"first","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, G211 Rollins Research Center, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaja","family":"Murali-Krishna","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, G211 Rollins Research Center, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Altman","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, G211 Rollins Research Center, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafi","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, G211 Rollins Research Center, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2000,3,29]]},"reference":[{"key":"p_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5258.54"},{"key":"p_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.160.2.521"},{"key":"p_3","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.62.6.2102-2106.1988","article-title":"T4+ T helper cell function in vivo: di\u00a1erential requirement for induction of anti viral cytotoxic T cell and antibody responses","volume":"62","author":"Ahmed R.","year":"1988","journal-title":"J. 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Series B: Biological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rstb.2000.0577","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rstb.2000.0577","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T21:27:11Z","timestamp":1778621231000},"score":1,"resource":{"primary":{"URL":"http:\/\/royalsocietypublishing.org\/rstb\/article\/355\/1395\/373-379\/19580"}},"subtitle":[],"editor":[{"given":"A. J.","family":"McMichael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"P. C.","family":"Doherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2000,3,29]]},"references-count":47,"journal-issue":{"issue":"1395","published-print":{"date-parts":[[2000,3,29]]}},"alternative-id":["10.1098\/rstb.2000.0577"],"URL":"https:\/\/doi.org\/10.1098\/rstb.2000.0577","relation":{},"ISSN":["0962-8436","1471-2970"],"issn-type":[{"value":"0962-8436","type":"print"},{"value":"1471-2970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,3,29]]}}}