{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:54:48Z","timestamp":1789674888738,"version":"4.0.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2012,12,1]],"date-time":"2012-12-01T00:00:00Z","timestamp":1354320000000},"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":[[2012,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The generation of CD4+ T cell memory cells is poorly understood. Recently, two different murine CD4+ TCR transgenic T cell lines, LLO118 and LLO56, both specific for the same epitope but differing in their expression level of the cell surface protein CD5, were generated. Notably, these cell lines showed different behavior upon primary and secondary exposure to Listeria monocytogenes. Whereas LLO118 showed a stronger primary response and generated more robust CD8+ T cell help upon secondary exposure, LLO56 CD4+ T cells had a dramatically better recall response. Using different mathematical models, we analyzed the dynamics of the two CD4+ T cell lines in mice during infection with L. monocytogenes. Our models allowed the quantitative comparison of the two T cell lines and provided predictions for the conversion of naive T cells into memory cells. LLO118 CD4+ T cells are estimated to have a higher proliferation rate than LLO56 CD4+ T cells upon primary exposure. This difference can be explained by the lower expression level of CD5 on LLO118 CD4+ T cells. Furthermore, LLO56 memory cells are predicted to have a 3-fold longer half-life than LLO118 memory cells (t1\/2LLO118 \u2248 4.3 to 5 d and t1\/2LLO56 \u2248 11.5 to 13.9 d). Although both cell lines differ in their memory capabilities, our analysis indicates no difference in the rate at which memory cells are generated. Our results show that different CD5 expression levels influence the proliferation dynamics of activated naive CD4+ T cells while leaving the conversion rate of those cells into memory cells unaffected.<\/jats:p>","DOI":"10.4049\/jimmunol.1200666","type":"journal-article","created":{"date-parts":[[2012,10,25]],"date-time":"2012-10-25T00:31:57Z","timestamp":1351125117000},"page":"5250-5256","source":"Crossref","is-referenced-by-count":9,"title":["Dynamics of CD4+ T Cell Responses against\n                    <i>Listeria monocytogenes<\/i>"],"prefix":"10.1093","volume":"189","author":[{"given":"Frederik","family":"Graw","sequence":"first","affiliation":[{"name":"Theoretical Biology and Biophysics, Los Alamos National Laboratory , Los Alamos, NM 87545"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K Scott","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S","family":"Perelson","sequence":"additional","affiliation":[{"name":"Theoretical Biology and Biophysics, Los Alamos National Laboratory , Los Alamos, NM 87545"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,12,1]]},"reference":[{"key":"2025032409365541300_r1","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/nri2619","article-title":"The precursors of memory: models and controversies","volume":"9","author":"Ahmed","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"2025032409365541300_r2","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.immuni.2009.11.007","article-title":"Diversity in T cell memory: an embarrassment of riches","volume":"31","author":"Jameson","year":"2009","journal-title":"Immunity"},{"key":"2025032409365541300_r3","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/ni.2041","article-title":"Understand memory, design better vaccines","volume":"12","author":"Bevan","year":"2011","journal-title":"Nat. Immunol."},{"key":"2025032409365541300_r4","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/ni.2039","article-title":"Immunological mechanisms of vaccination","volume":"12","author":"Pulendran","year":"2011","journal-title":"Nat. Immunol."},{"key":"2025032409365541300_r5","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1038\/ni1129","article-title":"Cognate CD4(+) T cell licensing of dendritic cells in CD8(+) T cell immunity","volume":"5","author":"Smith","year":"2004","journal-title":"Nat. Immunol."},{"key":"2025032409365541300_r6","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1126\/science.1083317","article-title":"Defective CD8 T cell memory following acute infection without CD4 T cell help","volume":"300","author":"Sun","year":"2003","journal-title":"Science"},{"key":"2025032409365541300_r7","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1126\/science.1082305","article-title":"Requirement for CD4 T cell help in generating functional CD8 T cell memory","volume":"300","author":"Shedlock","year":"2003","journal-title":"Science"},{"key":"2025032409365541300_r8","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/nature01441","article-title":"CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes","volume":"421","author":"Janssen","year":"2003","journal-title":"Nature"},{"key":"2025032409365541300_r9","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/nri1461","article-title":"Immune responses to Listeria monocytogenes","volume":"4","author":"Pamer","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"2025032409365541300_r10","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/ni1105","article-title":"CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection","volume":"5","author":"Sun","year":"2004","journal-title":"Nat. Immunol."},{"key":"2025032409365541300_r11","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/nature06672","article-title":"Memory CD4 T cells emerge from effector T-cell progenitors","volume":"452","author":"Harrington","year":"2008","journal-title":"Nature"},{"key":"2025032409365541300_r12","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1084\/jem.20071855","article-title":"Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors","volume":"205","author":"L\u00f6hning","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025032409365541300_r13","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.immuni.2007.08.007","article-title":"Heterogeneity and cell-fate decisions in effector and memory CD8+ T cell differentiation during viral infection","volume":"27","author":"Kaech","year":"2007","journal-title":"Immunity"},{"key":"2025032409365541300_r14","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.1365-2567.2010.03260.x","article-title":"Memory CD4 T cells: generation, reactivation and re-assignment","volume":"130","author":"MacLeod","year":"2010","journal-title":"Immunology"},{"key":"2025032409365541300_r15","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.1365-2567.2010.03288.x","article-title":"Generation, persistence and plasticity of CD4 T-cell memories","volume":"130","author":"Lees","year":"2010","journal-title":"Immunology"},{"key":"2025032409365541300_r16","doi-asserted-by":"crossref","first-page":"9511","DOI":"10.1073\/pnas.1202408109","article-title":"Distinct CD4+ helper T cells involved in primary and secondary responses to infection","volume":"109","author":"Weber","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032409365541300_r17","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1126\/science.7542801","article-title":"A role for CD5 in TCR-mediated signal transduction and thymocyte selection","volume":"269","author":"Tarakhovsky","year":"1995","journal-title":"Science"},{"key":"2025032409365541300_r18","doi-asserted-by":"crossref","first-page":"47","DOI":"10.4049\/jimmunol.146.1.47","article-title":"Induction of human T cell proliferation by a monoclonal antibody to CD5","volume":"146","author":"Spertini","year":"1991","journal-title":"J. Immunol."},{"key":"2025032409365541300_r19","doi-asserted-by":"crossref","first-page":"5464","DOI":"10.4049\/jimmunol.166.9.5464","article-title":"Fine tuning of TCR signaling by CD5","volume":"166","author":"Azzam","year":"2001","journal-title":"J. Immunol."},{"key":"2025032409365541300_r20","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1084\/jem.188.12.2301","article-title":"CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity","volume":"188","author":"Azzam","year":"1998","journal-title":"J. Exp. Med."},{"key":"2025032409365541300_r21","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/icb.2011.5","article-title":"Signaling thresholds govern heterogeneity in IL-7-receptor-mediated responses of na\u00efve CD8(+) T cells","volume":"89","author":"Palmer","year":"2011","journal-title":"Immunol. Cell Biol."},{"key":"2025032409365541300_r22","doi-asserted-by":"crossref","first-page":"10663","DOI":"10.1128\/JVI.75.22.10663-10669.2001","article-title":"Recruitment times, proliferation, and apoptosis rates during the CD8(+) T-cell response to lymphocytic choriomeningitis virus","volume":"75","author":"De Boer","year":"2001","journal-title":"J. Virol."},{"key":"2025032409365541300_r23","doi-asserted-by":"crossref","first-page":"3928","DOI":"10.4049\/jimmunol.171.8.3928","article-title":"Different dynamics of CD4+ and CD8+ T cell responses during and after acute lymphocytic choriomeningitis virus infection","volume":"171","author":"De Boer","year":"2003","journal-title":"J. Immunol."},{"key":"2025032409365541300_r24","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.jtbi.2006.10.017","article-title":"Mathematically modeling dynamics of T cell responses: predictions concerning the generation of memory cells","volume":"245","author":"Kohler","year":"2007","journal-title":"J. Theor. Biol."},{"key":"2025032409365541300_r25","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.4049\/jimmunol.168.4.1682","article-title":"Continued antigen stimulation is not required during CD4(+) T cell clonal expansion","volume":"168","author":"Lee","year":"2002","journal-title":"J. Immunol."},{"key":"2025032409365541300_r26","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.4049\/jimmunol.168.4.1528","article-title":"Cutting edge: CD4 and CD8 T cells are intrinsically different in their proliferative responses","volume":"168","author":"Foulds","year":"2002","journal-title":"J. Immunol."},{"key":"2025032409365541300_r27","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.4049\/jimmunol.168.4.1723","article-title":"Repeated antigen exposure is necessary for the differentiation, but not the initial proliferation, of naive CD4(+) T cells","volume":"168","author":"Baj\u00e9noff","year":"2002","journal-title":"J. Immunol."},{"key":"2025032409365541300_r28","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/90950","article-title":"Differential regulation of antiviral T-cell immunity results in stable CD8+ but declining CD4+ T-cell memory","volume":"7","author":"Homann","year":"2001","journal-title":"Nat. Med."},{"key":"2025032409365541300_r29","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1126\/science.1139393","article-title":"Asymmetric T lymphocyte division in the initiation of adaptive immune responses","volume":"315","author":"Chang","year":"2007","journal-title":"Science"},{"key":"2025032409365541300_r30","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/S0952-7915(99)00056-4","article-title":"From synapses to immunological memory: the role of sustained T cell stimulation","volume":"12","author":"Lanzavecchia","year":"2000","journal-title":"Curr. Opin. Immunol."},{"key":"2025032409365541300_r31","volume-title":"R: A Language and Environment for Statistical Computing.","author":"R Development Core Team","year":"2006"},{"key":"2025032409365541300_r32","volume-title":"Statistical Methods in Medical Research","author":"Armitage","year":"1994","edition":"2nd Ed."},{"key":"2025032409365541300_r33","doi-asserted-by":"crossref","first-page":"869","DOI":"10.4049\/jimmunol.177.2.869","article-title":"Divergent generation of heterogeneous memory CD4 T cells","volume":"177","author":"Moulton","year":"2006","journal-title":"J. Immunol."},{"key":"2025032409365541300_r34","doi-asserted-by":"crossref","first-page":"6704","DOI":"10.4049\/jimmunol.179.10.6704","article-title":"Strength of stimulus and clonal competition impact the rate of memory CD8 T cell differentiation","volume":"179","author":"Sarkar","year":"2007","journal-title":"J. Immunol."},{"key":"2025032409365541300_r35","doi-asserted-by":"crossref","first-page":"5548","DOI":"10.1182\/blood-2010-06-292748","article-title":"T-cell receptor signals direct the composition and function of the memory CD8+ T-cell pool","volume":"116","author":"Smith-Garvin","year":"2010","journal-title":"Blood"},{"key":"2025032409365541300_r36","doi-asserted-by":"crossref","first-page":"5560","DOI":"10.1182\/blood-2010-06-292458","article-title":"Loss of tonic T-cell receptor signals alters the generation but not the persistence of CD8+ memory T cells","volume":"116","author":"Wiehagen","year":"2010","journal-title":"Blood"},{"key":"2025032409365541300_r37","doi-asserted-by":"crossref","first-page":"e14502","DOI":"10.1371\/journal.pone.0014502","article-title":"Increased memory conversion of na\u00efve CD8 T cells activated during late phases of acute virus infection due to decreased cumulative antigen exposure","volume":"6","author":"Fousteri","year":"2011","journal-title":"PLoS ONE"},{"key":"2025032409365541300_r38","doi-asserted-by":"crossref","first-page":"777","DOI":"10.4049\/jimmunol.177.2.777","article-title":"Cutting edge: latecomer CD8 T cells are imprinted with a unique differentiation program","volume":"177","author":"D\u2019Souza","year":"2006","journal-title":"J. Immunol."},{"key":"2025032409365541300_r39","doi-asserted-by":"crossref","first-page":"5341","DOI":"10.4049\/jimmunol.174.9.5341","article-title":"Reducing the stimulation of CD8+ T cells during infection with intracellular bacteria promotes differentiation primarily into a central (CD62LhighCD44high) subset","volume":"174","author":"van Faassen","year":"2005","journal-title":"J. Immunol."},{"key":"2025032409365541300_r40","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/icb.2011.28","article-title":"Regulators of T-cell memory generation: TCR signals versus CD4+ help?","volume":"89","author":"Umeshappa","year":"2011","journal-title":"Immunol. Cell Biol."},{"key":"2025032409365541300_r41","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.immuni.2008.02.014","article-title":"Rapid culling of the CD4+ T cell repertoire in the transition from effector to memory","volume":"28","author":"Williams","year":"2008","journal-title":"Immunity"},{"key":"2025032409365541300_r42","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1084\/jem.20042521","article-title":"Antigen persistence is required throughout the expansion phase of a CD4(+) T cell response","volume":"201","author":"Obst","year":"2005","journal-title":"J. Exp. Med."},{"key":"2025032409365541300_r43","doi-asserted-by":"crossref","first-page":"6545","DOI":"10.4049\/jimmunol.1001867","article-title":"Reduced functional avidity promotes central and effector memory CD4 T cell responses to tumor-associated antigens","volume":"185","author":"Caserta","year":"2010","journal-title":"J. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/189\/11\/5250\/62480869\/1200666.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/189\/11\/5250\/62480869\/1200666.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T05:24:36Z","timestamp":1743053076000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/189\/11\/5250\/7998966"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,1]]},"references-count":43,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2012,12,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1200666","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,12]]},"published":{"date-parts":[[2012,12,1]]}}}