{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T20:01:18Z","timestamp":1762459278811},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2015,3,24]],"date-time":"2015-03-24T00:00:00Z","timestamp":1427155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0119200","type":"journal-article","created":{"date-parts":[[2015,3,24]],"date-time":"2015-03-24T20:38:30Z","timestamp":1427229510000},"page":"e0119200","update-policy":"http:\/\/dx.doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Programmed Death 1 Regulates Memory Phenotype CD4 T Cell Accumulation, Inhibits Expansion of the Effector Memory Phenotype Subset and Modulates Production of Effector Cytokines"],"prefix":"10.1371","volume":"10","author":[{"given":"Joanna J.","family":"Charlton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debbie","family":"Tsoukatou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clio","family":"Mamalaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Chatzidakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2015,3,24]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/ni.2018","article-title":"Normal T cell homeostasis: the conversion of naive cells into memory-phenotype cells","volume":"131","author":"J Sprent","year":"2011","journal-title":"Nat Immunol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.clim.2005.09.012","article-title":"Commensal microbiota alter the abundance and TCR responsiveness of splenic naive CD4+ T lymphocytes","volume":"117","author":"T Huang","year":"2005","journal-title":"Clin Immunol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1084\/jem.20081829","article-title":"The antigen-specific CD8+ T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansion","volume":"206","author":"C Haluszczak","year":"2009","journal-title":"J Exp Med"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.immuni.2012.10.021","article-title":"Virus-specific CD4(+) memory-phenotype T cells are abundant in unexposed adults","volume":"38","author":"LF Su","year":"2013","journal-title":"Immunity"},{"key":"ref5","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":"SC Jameson","year":"2009","journal-title":"Immunity"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.coi.2005.04.010","article-title":"Understanding the generation and function of memory T cell subsets","volume":"17","author":"A Lanzavecchia","year":"2005","journal-title":"Curr Opin Immunol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nri3442","article-title":"The integration of T cell migration, differentiation and function","volume":"13","author":"D Masopust","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"5788","DOI":"10.4049\/jimmunol.1203111","article-title":"Homeostatic Proliferation of Naive CD4+ T Cells in Mesenteric Lymph Nodes Generates Gut-Tropic Th17 Cells","volume":"190","author":"T Kawabe","year":"2013","journal-title":"The Journal of Immunology"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1002\/eji.200526004","article-title":"Novel phenotypes and migratory properties distinguish memory CD4 T cell subsets in lymphoid and lung tissue","volume":"35","author":"AW Bingaman","year":"2005","journal-title":"Eur J Immunol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s12026-013-8448-1","article-title":"Autoimmune effector memory T cells: the bad and the good","volume":"57","author":"P Devarajan","year":"2013","journal-title":"Immunol Res"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"774","DOI":"10.4049\/jimmunol.180.2.774","article-title":"ICOS controls the pool size of effector-memory and regulatory T cells","volume":"180","author":"Y Burmeister","year":"2008","journal-title":"J Immunol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"5014","DOI":"10.4049\/jimmunol.179.8.5014","article-title":"Differential requirements for OX40 signals on generation of effector and central memory CD4+ T cells","volume":"179","author":"P Soroosh","year":"2007","journal-title":"J Immunol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1600-065X.2010.00923.x","article-title":"The PD-1 pathway in tolerance and autoimmunity","volume":"236","author":"LM Francisco","year":"2010","journal-title":"Immunol Rev"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1093\/intimm\/dxm057","article-title":"PD-1 and PD-1 ligands: from discovery to clinical application","volume":"19","author":"T Okazaki","year":"2007","journal-title":"Int Immunol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/ni1443","article-title":"The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection","volume":"8","author":"AH Sharpe","year":"2007","journal-title":"Nat Immunol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1111\/j.1474-9726.2010.00611.x","article-title":"Partial restoration of T-cell function in aged mice by in vitro blockade of the PD-1\/ PD-L1 pathway","volume":"9","author":"CS Lages","year":"2010","journal-title":"Aging Cell"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.mad.2009.08.006","article-title":"Advancing age leads to predominance of inhibitory receptor expressing CD4 T cells","volume":"130","author":"R Channappanavar","year":"2009","journal-title":"Mech Ageing Dev"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"6104","DOI":"10.4049\/jimmunol.1201617","article-title":"Programmed death-1 shapes memory phenotype CD8 T cell subsets in a cell-intrinsic manner","volume":"190","author":"JJ Charlton","year":"2013","journal-title":"J Immunol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1093\/intimm\/10.10.1563","article-title":"Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses","volume":"10","author":"H Nishimura","year":"1998","journal-title":"Int Immunol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1002\/immu.200310005","article-title":"Transgenic mice with hematopoietic and lymphoid specific expression of Cre","volume":"33","author":"J de Boer","year":"2003","journal-title":"Eur J Immunol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nature05597","article-title":"Tyrosine kinase receptor RET is a key regulator of Peyer&apos;s patch organogenesis","volume":"446","author":"H Veiga-Fernandes","year":"2007","journal-title":"Nature"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"6735","DOI":"10.4049\/jimmunol.178.11.6735","article-title":"An essential role for TNF in modulating thresholds for survival, activation, and tolerance of CD8+ T cells","volume":"178","author":"I Chatzidakis","year":"2007","journal-title":"J Immunol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/ni1227","article-title":"Initial T cell frequency dictates memory CD8+ T cell lineage commitment","volume":"6","author":"AL Marzo","year":"2005","journal-title":"Nat Immunol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"3561","DOI":"10.1002\/eji.200526347","article-title":"PD-L2:PD-1 involvement in T cell proliferation, cytokine production, and integrin-mediated adhesion","volume":"35","author":"PA Saunders","year":"2005","journal-title":"Eur J Immunol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.exger.2009.05.003","article-title":"Age-associated up-regulation of a negative co-stimulatory receptor PD-1 in mouse CD4+ T cells","volume":"44","author":"Y Shimada","year":"2009","journal-title":"Exp Gerontol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/ni946","article-title":"Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory cells","volume":"4","author":"B Seddon","year":"2003","journal-title":"Nat Immunol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"7409","DOI":"10.1073\/pnas.1118539109","article-title":"Type II membrane protein CD69 regulates the formation of resting T-helper memory","volume":"109","author":"K Shinoda","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nature04606","article-title":"CD69 acts downstream of interferon-alpha\/beta to inhibit S1P1 and lymphocyte egress from lymphoid organs","volume":"440","author":"LR Shiow","year":"2006","journal-title":"Nature"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"15807","DOI":"10.1073\/pnas.0908805106","article-title":"PD-1+ memory phenotype CD4+ T cells expressing C\/EBPalpha underlie T cell immunodepression in senescence and leukemia","volume":"106","author":"K Shimatani","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nri3567","article-title":"Human memory T cells: generation, compartmentalization and homeostasis","volume":"14","author":"DL Farber","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nri1807","article-title":"Diversification of T-helper-cell lineages: finding the family root of IL-17-producing cells","volume":"6","author":"C Dong","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.immuni.2007.07.007","article-title":"Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude","volume":"27","author":"JJ Moon","year":"2007","journal-title":"Immunity"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"6544","DOI":"10.4049\/jimmunol.180.10.6544","article-title":"Naive and innate memory phenotype CD4+ T cells have different requirements for active Itk for their development","volume":"180","author":"J Hu","year":"2008","journal-title":"J Immunol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.immuni.2008.11.002","article-title":"Homeostasis of naive and memory T cells","volume":"29","author":"CD Surh","year":"2008","journal-title":"Immunity"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1002\/eji.200939444","article-title":"Homeostatic proliferation and survival of naive and memory T cells","volume":"39","author":"O Boyman","year":"2009","journal-title":"Eur J Immunol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1084\/jem.20030735","article-title":"Interleukin 7 Regulates the Survival and Generation of Memory CD4 Cells","volume":"198","author":"RM Kondrack","year":"2003","journal-title":"The Journal of Experimental Medicine"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0092-8674(04)00335-6","article-title":"Homeostatic Expansion of T Cells during Immune Insufficiency Generates Autoimmunity","volume":"117","author":"C King","journal-title":"Cell"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"61","DOI":"10.4049\/jimmunol.171.1.61","article-title":"Homeostasis of naive and memory CD4+ T cells: IL-2 and IL-7 differentially regulate the balance between proliferation and Fas-mediated apoptosis","volume":"171","author":"S Jaleco","year":"2003","journal-title":"J Immunol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"9357","DOI":"10.1073\/pnas.0400640101","article-title":"IL-7 regulates basal homeostatic proliferation of antiviral CD4+T cell memory","volume":"101","author":"DC Lenz","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1084\/jem.20030725","article-title":"IL-7 promotes the transition of CD4 effectors to persistent memory cells","volume":"198","author":"J Li","year":"2003","journal-title":"J Exp Med"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"e16529","DOI":"10.1371\/journal.pone.0016529","article-title":"Protective effector memory CD4 T cells depend on ICOS for survival","volume":"6","author":"TV Moore","year":"2011","journal-title":"PLoS One"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/ni.2038","article-title":"Origins of CD4(+) effector and central memory T cells","volume":"12","author":"M Pepper","year":"2011","journal-title":"Nat Immunol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1093\/intimm\/dxq446","article-title":"PD-1\u2013PD-L1 pathway impairs Th1 immune response in the late stage of infection with Mycobacterium bovis bacillus Calmette\u2013Gu\u00e9rin","volume":"22","author":"S Sakai","year":"2010","journal-title":"International Immunology"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/ni.2180","article-title":"Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection","volume":"13","author":"NS Butler","year":"2012","journal-title":"Nat Immunol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"21182","DOI":"10.1073\/pnas.1118450109","article-title":"Antigen-specific CD4 T-cell help rescues exhausted CD8 T cells during chronic viral infection","volume":"108","author":"RD Aubert","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/nm.2612","article-title":"Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans","volume":"18","author":"TM Wilkinson","year":"2012","journal-title":"Nat Med"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1615\/CritRevImmunol.v32.i2.10","article-title":"Central and effector memory CD4 and CD8 T-cell responses to tumor-associated antigens","volume":"32","author":"S Caserta","year":"2012","journal-title":"Crit Rev Immunol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0119200","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T01:46:35Z","timestamp":1540345595000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0119200"}},"subtitle":[],"editor":[{"given":"Derya","family":"Unutmaz","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,3,24]]},"references-count":47,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,3,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0119200","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,24]]}}}