{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:28:18Z","timestamp":1791217698173,"version":"4.1.0"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2008,4,11]],"date-time":"2008-04-11T00:00:00Z","timestamp":1207872000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1000041","type":"journal-article","created":{"date-parts":[[2008,4,10]],"date-time":"2008-04-10T17:39:11Z","timestamp":1207849151000},"page":"e1000041","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":71,"title":["Tentative T Cells: Memory Cells Are Quick to Respond, but Slow to Divide"],"prefix":"10.1371","volume":"4","author":[{"given":"Jason K.","family":"Whitmire","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boreth","family":"Eam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Lindsay","family":"Whitton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2008,4,11]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/76907","article-title":"Response of naive and memory CD8+ T cells to antigen stimulation in vivo.","volume":"1","author":"H Veiga-Fernandes","year":"2000","journal-title":"Nat Immunol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.4049\/jimmunol.164.5.2338","article-title":"Qualitative changes accompany memory T cell generation: faster, more effective responses at lower doses of antigen.","volume":"164","author":"PR Rogers","year":"2000","journal-title":"J Immunol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/90650","article-title":"Functional avidity maturation of CD8<sup>+<\/sup> T cells without selection of higher affinity TCR.","volume":"2","author":"MK Slifka","year":"2001","journal-title":"Nat Immunol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.0105-2896.2006.00393.x","article-title":"Development, trafficking, and function of memory T-cell subsets.","volume":"211","author":"L Lefrancois","year":"2006","journal-title":"Immunol Rev"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1084\/jem.194.7.953","article-title":"Migratory properties of naive, effector, and memory CD8<sup>+<\/sup> T cells.","volume":"194","author":"W Weninger","year":"2001","journal-title":"J Exp Med"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.4049\/jimmunol.176.5.3028","article-title":"Precursor frequency, nonlinear proliferation, and functional maturation of virus-specific CD4<sup>+<\/sup> T cells.","volume":"176","author":"JK Whitmire","year":"2006","journal-title":"J Immunol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"6032","DOI":"10.4049\/jimmunol.171.11.6032","article-title":"Activation of antigen-specific CD8 T cells results in minimal killing of bystander bacteria.","volume":"171","author":"J Jiang","year":"2003","journal-title":"J Immunol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"248","DOI":"10.4049\/jimmunol.172.1.248","article-title":"T cell clonal conditioning: a phase occurring early after antigen presentation but before clonal expansion is impacted by Toll-like receptor stimulation.","volume":"172","author":"JR Maxwell","year":"2004","journal-title":"J Immunol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1084\/jem.20040769","article-title":"Type I interferon sensitizes lymphocytes to apoptosis and reduces resistance to Listeria infection.","volume":"200","author":"JA Carrero","year":"2004","journal-title":"J Exp Med"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/ni969","article-title":"Similarities and differences in CD4+ and CD8+ effector and memory T cell generation.","volume":"4","author":"RA Seder","year":"2003","journal-title":"Nat Immunol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.4049\/jimmunol.176.7.4083","article-title":"Rapid demethylation of the IFN-gamma gene occurs in memory but not naive CD8 T cells.","volume":"176","author":"EN Kersh","year":"2006","journal-title":"J Immunol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"208","DOI":"10.4049\/jimmunol.164.1.208","article-title":"Activated and memory CD8<sup>+<\/sup> T cells can be distinguished by their cytokine profiles and phenotypic markers.","volume":"164","author":"MK Slifka","year":"2000","journal-title":"J Immunol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"4875","DOI":"10.4049\/jimmunol.172.8.4875","article-title":"Activated primary and memory CD8 T cells migrate to nonlymphoid tissues regardless of site of activation or tissue of origin.","volume":"172","author":"D Masopust","year":"2004","journal-title":"J Immunol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1126\/science.1058867","article-title":"Preferential localization of effector memory cells in nonlymphoid tissue.","volume":"291","author":"D Masopust","year":"2001","journal-title":"Science"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1084\/jem.20021052","article-title":"CD4 effector T cell subsets in the response to influenza: heterogeneity, migration, and function.","volume":"196","author":"E Roman","year":"2002","journal-title":"J Exp Med"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/ni889","article-title":"Lineage relationship and protective immunity of memory CD8 T cell subsets.","volume":"4","author":"EJ Wherry","year":"2003","journal-title":"Nat Immunol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"7732","DOI":"10.4049\/jimmunol.174.12.7732","article-title":"The functional heterogeneity of type 1 effector T cells in response to infection is related to the potential for IFN-gamma production.","volume":"174","author":"KD Mayer","year":"2005","journal-title":"J Immunol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"5936","DOI":"10.4049\/jimmunol.174.10.5936","article-title":"Cutting Edge: Re-evaluating the <italic>in vivo<\/italic> cytokine responses of CD8<sup>+<\/sup> T cells during primary and secondary viral infections.","volume":"174","author":"F Liu","year":"2005","journal-title":"J Immunol"},{"key":"ref19","first-page":"1","article-title":"Detection of Intracellular Cytokines by Flow Cytometry.","author":"B Foster","year":"2007"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/nature02238","article-title":"T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases.","volume":"427","author":"TR Mempel","year":"2004","journal-title":"Nature"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"12703","DOI":"10.1128\/JVI.79.20.12703-12713.2005","article-title":"Rapid recruitment of virus-specific CD8 T cells restructures immunodominance during protective secondary responses.","volume":"79","author":"AE Tebo","year":"2005","journal-title":"J Virol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.4049\/jimmunol.168.4.1682","article-title":"Continued antigen stimulation is not required during CD4<sup>+<\/sup> T cell clonal expansion.","volume":"168","author":"WT Lee","year":"2002","journal-title":"J Immunol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1172\/JCI119873","article-title":"Following the fate of individual T cells throughout activation and clonal expansion. Signals from T cell receptor and CD28 differentially regulate the induction and duration of a proliferative response.","volume":"100","author":"AD Wells","year":"1997","journal-title":"J Clin Invest"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1084\/jem.186.6.859","article-title":"Rapid effector function in CD8<sup>+<\/sup> memory T cells.","volume":"186","author":"A Lalvani","year":"1997","journal-title":"J Exp Med"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.1073\/pnas.96.6.2976","article-title":"Functional differences between memory and na\u00efve CD8 T cells.","volume":"96","author":"BK Cho","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/(SICI)1521-4141(199901)29:01<284::AID-IMMU284>3.0.CO;2-C","article-title":"Kinetics of the response of naive and memory CD8 T cells to antigen: similarities and differences.","volume":"29","author":"C Zimmermann","year":"1999","journal-title":"Eur J Immunol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"3760","DOI":"10.4049\/jimmunol.169.7.3760","article-title":"Differential sensitivity of naive and memory CD8+ T cells to apoptosis in vivo.","volume":"169","author":"JM Grayson","year":"2002","journal-title":"J Immunol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"4933","DOI":"10.4049\/jimmunol.170.10.4933","article-title":"Regulation of CD8<sup>+<\/sup> T cells undergoing primary and secondary responses to infection in the same host.","volume":"170","author":"VP Badovinac","year":"2003","journal-title":"J Immunol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.4049\/jimmunol.177.3.1411","article-title":"Cutting edge: central memory T cells do not show accelerated proliferation or tissue infiltration in response to localized herpes simplex virus-1 infection.","volume":"177","author":"AT Stock","year":"2006","journal-title":"J Immunol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.4049\/jimmunol.166.3.1813","article-title":"Activated antigen-specific CD8<sup>+<\/sup> T cells persist in the lungs following recovery from respiratory virus infections.","volume":"166","author":"RJ Hogan","year":"2001","journal-title":"J Immunol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1084\/jem.20050227","article-title":"Unexpected prolonged presentation of influenza antigens promotes CD4 T cell memory generation.","volume":"202","author":"DM Jelley-Gibbs","year":"2005","journal-title":"J Exp Med"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1084\/jem.20050137","article-title":"Differential contributions of central and effector memory T cells to recall responses.","volume":"202","author":"AD Roberts","year":"2005","journal-title":"The Journal of Experimental Medicine"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.immuni.2006.01.015","article-title":"Residual antigen presentation after influenza virus infection affects CD8 T cell activation and migration.","volume":"24","author":"DJ Zammit","year":"2006","journal-title":"Immunity"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"537","DOI":"10.4049\/jimmunol.176.1.537","article-title":"Memory T cell populations in the lung airways are maintained by continual recruitment.","volume":"176","author":"KH Ely","year":"2006","journal-title":"J Immunol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S1074-7613(00)80091-6","article-title":"Following the development of a CD4 T cell response in vivo: from activation to memory formation.","volume":"11","author":"S Garcia","year":"1999","journal-title":"Immunity"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"6659","DOI":"10.4049\/jimmunol.169.12.6659","article-title":"Cutting edge: B7\/CD28 interactions regulate cell cycle progression independent of the strength of TCR signaling.","volume":"169","author":"JL Bonnevier","year":"2002","journal-title":"J Immunol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"3777","DOI":"10.4049\/jimmunol.168.8.3777","article-title":"Temporal segregation of 4-1BB versus CD28-mediated costimulation: 4-1BB ligand influences T cell numbers late in the primary response and regulates the size of the T cell memory response following influenza infection.","volume":"168","author":"EM Bertram","year":"2002","journal-title":"J Immunol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S1074-7613(01)00191-1","article-title":"OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells.","volume":"15","author":"PR Rogers","year":"2001","journal-title":"Immunity"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"4746","DOI":"10.4049\/jimmunol.156.12.4746","article-title":"Characterization of early IL-12, IFN-\u03b1\/\u03b2, and TNF effects on antiviral state and NK cell responses during murine cytomegalovirus infection.","volume":"156","author":"JS Orange","year":"1996","journal-title":"J Immunol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.1002\/1521-4141(2001010)31:10<3048::AID-IMMU3048>3.0.CO;2-1","article-title":"NK cell functions restrain T cell responses during viral infections.","volume":"31","author":"HC Su","year":"2001","journal-title":"Eur J Immunol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/sj.emboj.7601520","article-title":"Metalloproteases regulate T-cell proliferation and effector function via LAG-3.","volume":"26","author":"N Li","year":"2007","journal-title":"EMBO J"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1084\/jem.20041463","article-title":"Interferon-\u03b3 acts directly on CD8<sup>+<\/sup> T cells to increase their abundance during virus infection.","volume":"201","author":"JK Whitmire","year":"2005","journal-title":"J Exp Med"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"5624","DOI":"10.4049\/jimmunol.175.9.5624","article-title":"Cutting Edge: Early IFN-\u03b3 signaling directly enhances primary antiviral CD4<sup>+<\/sup> T cell responses.","volume":"175","author":"JK Whitmire","year":"2005","journal-title":"J Immunol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.4049\/jimmunol.176.6.3315","article-title":"Cutting Edge: The direct action of type I IFN on CD4 T cells is critical for sustaining clonal expansion in response to a viral but not a bacterial infection.","volume":"176","author":"C Havenar-Daughton","year":"2006","journal-title":"J Immunol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1084\/jem.20050821","article-title":"Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection.","volume":"202","author":"GA Kolumam","year":"2005","journal-title":"J Exp Med"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1099\/0022-1317-82-8-1971","article-title":"Perforin and Fas in murine gammaherpesvirus-specific CD8(+) T cell control and morbidity.","volume":"82","author":"DJ Topham","year":"2001","journal-title":"J Gen Virol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1093\/intimm\/dxh168","article-title":"Functional T cells in primary immune response to histoplasmosis.","volume":"16","author":"JS Lin","year":"2004","journal-title":"Int Immunol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.4049\/jimmunol.172.6.3491","article-title":"Prolonged antigen presentation, APC-, and CD8+ T cell turnover during mycobacterial infection: comparison with Listeria monocytogenes.","volume":"172","author":"H van Faassen","year":"2004","journal-title":"J Immunol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1084\/jem.192.1.117","article-title":"Interferon gamma eliminates responding CD4 T cells during mycobacterial infection by inducing apoptosis of activated CD4 T cells.","volume":"192","author":"DK Dalton","year":"2000","journal-title":"J Exp Med"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"925","DOI":"10.4049\/jimmunol.177.2.925","article-title":"Antigen-experienced T cells limit the priming of naive T cells during infection with Leishmania major.","volume":"177","author":"PM Gray","year":"2006","journal-title":"J Immunol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"6265","DOI":"10.4049\/jimmunol.173.10.6265","article-title":"Differential regulation of primary and secondary CD8+ T cells in the central nervous system.","volume":"173","author":"C Ramakrishna","year":"2004","journal-title":"J Immunol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.4049\/jimmunol.167.5.2753","article-title":"Concurrent naive and memory CD8(+) T cell responses to an influenza A virus.","volume":"167","author":"SJ Turner","year":"2001","journal-title":"J Immunol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1084\/jem.20060995","article-title":"Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection.","volume":"203","author":"V Vezys","year":"2006","journal-title":"J Exp Med"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.4049\/jimmunol.170.9.4745","article-title":"Mitochondrial potential and reactive oxygen intermediates in antigen-specific CD8<sup>+<\/sup> T cells during viral infection.","volume":"170","author":"JM Grayson","year":"2003","journal-title":"J Immunol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/ni804","article-title":"Programmed contraction of CD8<sup>+<\/sup> T cells after infection.","volume":"3","author":"VP Badovinac","year":"2002","journal-title":"Nat Immunol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"5679","DOI":"10.4049\/jimmunol.173.9.5679","article-title":"Duration of infection and antigen display have minimal influence on the kinetics of the CD4<sup>+<\/sup> T cell response to Listeria monocytogenes infection.","volume":"173","author":"GA Corbin","year":"2004","journal-title":"J Immunol"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"3950","DOI":"10.4049\/jimmunol.164.8.3950","article-title":"Cutting edge: increased expression of bcl-2 in antigen-specific memory CD8<sup>+<\/sup> T cells.","volume":"164","author":"JM Grayson","year":"2000","journal-title":"J Immunol"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1002\/(SICI)1521-4141(199801)28:01<390::AID-IMMU390>3.0.CO;2-O","article-title":"Virus-specific MHC-class II-restricted TCR-transgenic mice: effects on humoral and cellular immune responses after viral infection.","volume":"28","author":"A Oxenius","year":"1998","journal-title":"Eur J Immunol"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/342559a0","article-title":"Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen.","volume":"342","author":"H Pircher","year":"1989","journal-title":"Nature"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"8281","DOI":"10.1128\/JVI.72.10.8281-8288.1998","article-title":"Long-term CD4 Th1 and Th2 memory following acute lymphocytic choriomeningitis virus infection.","volume":"72","author":"JK Whitmire","year":"1998","journal-title":"J Virol"}],"container-title":["PLoS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1000041","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T12:19:57Z","timestamp":1684325997000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1000041"}},"subtitle":[],"editor":[{"given":"Richard A.","family":"Koup","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2008,4,11]]},"references-count":60,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2008,4,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1000041","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1109239.565247","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1109239.564766","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,4,11]]}}}