{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T18:33:24Z","timestamp":1778870004862,"version":"3.51.4"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2014,2,10]],"date-time":"2014-02-10T00:00:00Z","timestamp":1391990400000},"content-version":"unspecified","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.0088884","type":"journal-article","created":{"date-parts":[[2014,2,10]],"date-time":"2014-02-10T22:03:27Z","timestamp":1392069807000},"page":"e88884","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["Levels of CD56+TIM-3- Effector CD8 T Cells Distinguish HIV Natural Virus Suppressors from Patients Receiving Antiretroviral Therapy"],"prefix":"10.1371","volume":"9","author":[{"given":"Bhawna","family":"Poonia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. David","family":"Pauza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2014,2,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"5509","DOI":"10.1128\/JVI.73.7.5509-5519.1999","article-title":"Lack of viral escape and defective in vivo activation of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes in rapidly progressive infection","volume":"73","author":"CM Hay","year":"1999","journal-title":"J Virol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"7320","DOI":"10.1128\/JVI.74.16.7320-7330.2000","article-title":"Human immunodeficiency virus-specific circulating CD8 T lymphocytes have down-modulated CD3zeta and CD28, key signaling molecules for T-cell activation","volume":"74","author":"LA Trimble","year":"2000","journal-title":"J Virol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1097\/00002030-200404090-00003","article-title":"Granule-dependent mechanisms of lysis are defective in CD8 T cells of HIV-infected, antiretroviral therapy-treated individuals","volume":"18","author":"D Trabattoni","year":"2004","journal-title":"AIDS"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/1742-4690-8-63","article-title":"Viral suppression of multiple escape mutants by de novo CD8(+) T cell responses in a human immunodeficiency virus-1 infected elite suppressor","volume":"8","author":"KA O\u2032Connell","year":"2011","journal-title":"Retrovirology"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"5170","DOI":"10.1128\/JVI.02379-12","article-title":"HIV-Specific CD8+ T Cells from Elite Controllers Are Primed for Survival","volume":"87","author":"J Yan","year":"2013","journal-title":"J Virol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"4232","DOI":"10.1158\/1078-0432.CCR-07-4912","article-title":"Isopentenyl pyrophosphate-activated CD56+ {gamma}{delta} T lymphocytes display potent antitumor activity toward human squamous cell carcinoma","volume":"14","author":"AA Alexander","year":"2008","journal-title":"Clin Cancer Res"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/nri1711","article-title":"NK cells in HIV infection: paradigm for protection or targets for ambush","volume":"5","author":"AS Fauci","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.4049\/jimmunol.164.3.1148","article-title":"Cutting edge: cytolytic effector function in human circulating CD8+ T cells closely correlates with CD56 surface expression","volume":"164","author":"MJ Pittet","year":"2000","journal-title":"J Immunol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.imbio.2010.09.012","article-title":"IL-15 induces CD8+ T cells to acquire functional NK receptors capable of modulating cytotoxicity and cytokine secretion","volume":"216","author":"MP Correia","year":"2011","journal-title":"Immunobiology"},{"key":"ref10","first-page":"804s","article-title":"Expression of CD56 by human papillomavirus E7-specific CD8+ cytotoxic T lymphocytes correlates with increased intracellular perforin expression and enhanced cytotoxicity against HLA-A2-matched cervical tumor cells","volume":"7","author":"AD Santin","year":"2001","journal-title":"Clin Cancer Res"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1023\/A:1015476114409","article-title":"Selective depletion of CD56(dim) NK cell subsets and maintenance of CD56(bright) NK cells in treatment-naive HIV-1-seropositive individuals","volume":"22","author":"R Tarazona","year":"2002","journal-title":"J Clin Immunol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1097\/QAD.0b013e32832ff1ff","article-title":"Natural viral suppressors of HIV-1 have a unique capacity to maintain gammadelta T cells","volume":"23","author":"DJ Riedel","year":"2009","journal-title":"AIDS"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"3822","DOI":"10.1182\/blood-2009-06-226332","article-title":"The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer-cell subsets associated with high levels of HIV-1 viremia","volume":"114","author":"E Brunetta","year":"2009","journal-title":"Blood"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"2410","DOI":"10.1002\/eji.200324141","article-title":"The impaired NK cell cytolytic function in viremic HIV-1 infection is associated with a reduced surface expression of natural cytotoxicity receptors (NKp46, NKp30 and NKp44)","volume":"33","author":"A De Maria","year":"2003","journal-title":"Eur J Immunol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1006\/cimm.1999.1565","article-title":"Epinephrine-induced mobilization of natural killer (NK) cells and NK-like T cells in HIV-infected patients","volume":"197","author":"SR Sondergaard","year":"1999","journal-title":"Cell Immunol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"2886","DOI":"10.1073\/pnas.0409872102","article-title":"Characterization of CD56-\/CD16+ natural killer (NK) cells: a highly dysfunctional NK subset expanded in HIV-infected viremic individuals","volume":"102","author":"D Mavilio","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"15011","DOI":"10.1073\/pnas.2336091100","article-title":"Natural killer cells in HIV-1 infection: dichotomous effects of viremia on inhibitory and activating receptors and their functional correlates","volume":"100","author":"D Mavilio","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Chaudhry S, Cairo C, Venturi V, Pauza CD (2013) The gammadelta T cell receptor repertoire is reconstituted in HIV patients after prolonged antiretroviral therapy. AIDS.","DOI":"10.1097\/QAD.0b013e3283611888"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1097\/00002030-200201250-00008","article-title":"NK-associated receptors on CD8 T cells from treatment-naive HIV-infected individuals: defective expression of CD56","volume":"16","author":"R Tarazona","year":"2002","journal-title":"AIDS"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1189\/jlb.1207847","article-title":"Impacts of HIV infection on Vgamma2Vdelta2 T cell phenotype and function: a mechanism for reduced tumor immunity in AIDS","volume":"84","author":"JS Cummings","year":"2008","journal-title":"J Leukoc Biol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1093\/infdis\/jis217","article-title":"Impact of persistent HIV replication on CD4 negative Vgamma2Vdelta2 T cells","volume":"205","author":"S Boudova","year":"2012","journal-title":"J Infect Dis"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"e1000917","DOI":"10.1371\/journal.ppat.1000917","article-title":"Perforin expression directly ex vivo by HIV-specific CD8 T-cells is a correlate of HIV elite control","volume":"6","author":"AR Hersperger","year":"2010","journal-title":"PLoS Pathog"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"4928","DOI":"10.1182\/blood-2011-12-395186","article-title":"Chronic HIV infection affects the expression of the 2 transcription factors required for CD8 T-cell differentiation into cytolytic effectors","volume":"119","author":"P Ribeiro-dos-Santos","year":"2012","journal-title":"Blood"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1126\/science.1159806","article-title":"Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesodermin","volume":"321","author":"AM Intlekofer","year":"2008","journal-title":"Science"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"3799","DOI":"10.1182\/blood-2010-12-322727","article-title":"Increased HIV-specific CD8+ T-cell cytotoxic potential in HIV elite controllers is associated with T-bet expression","volume":"117","author":"AR Hersperger","year":"2011","journal-title":"Blood"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"12343","DOI":"10.1128\/JVI.05682-11","article-title":"HIV-1 infection abrogates CD8+ T cell mitogen-activated protein kinase signaling responses","volume":"85","author":"TQ Crawford","year":"2011","journal-title":"J Virol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"e77412","DOI":"10.1371\/journal.pone.0077412","article-title":"Activation Associated ERK1\/2 Signaling Impairments in CD8(+) T Cells Co-Localize with Blunted Polyclonal and HIV-1 Specific Effector Functions in Early Untreated HIV-1 Infection","volume":"8","author":"TQ Crawford","year":"2013","journal-title":"PLoS One"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1084\/jem.20081398","article-title":"Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection","volume":"205","author":"RB Jones","year":"2008","journal-title":"J Exp Med"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1038\/nm.2871","article-title":"Bat3 promotes T cell responses and autoimmunity by repressing Tim-3-mediated cell death and exhaustion","volume":"18","author":"M Rangachari","year":"2012","journal-title":"Nat Med"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1096\/fj.11-195180","article-title":"Rapid down-regulation of gammac on T cells in early SIV infection correlates with impairment of T-cell function","volume":"26","author":"H Xu","year":"2012","journal-title":"FASEB J"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1086\/383034","article-title":"Immune reconstitution in HIV-infected patients","volume":"38","author":"HH Hirsch","year":"2004","journal-title":"Clin Infect Dis"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1089\/aid.2008.0088","article-title":"HIV rebound after discontinuation of antiretroviral therapy increases and expands HIV-specific CD8+ responses but has no impact on its functionality","volume":"24","author":"M Lopez","year":"2008","journal-title":"AIDS Res Hum Retroviruses"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1002\/eji.200738054","article-title":"Suppression of viral replication with highly active antiretroviral therapy has no impact on the functional profile of HIV-specific CD8(+) T cells","volume":"38","author":"M Lopez","year":"2008","journal-title":"Eur J Immunol"},{"key":"ref34","first-page":"25","article-title":"Functional analysis of HIV-specific cytotoxic T lymphocytes in antiviral-treated- and-naive patients: a preliminary report","volume":"16","author":"D Trabattoni","year":"2002","journal-title":"J Biol Regul Homeost Agents"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1084\/jem.192.1.63","article-title":"HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function","volume":"192","author":"V Appay","year":"2000","journal-title":"J Exp Med"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1083\/jcb.110.1.193","article-title":"The neural cell adhesion molecule N-CAM enhances L1-dependent cell-cell interactions","volume":"110","author":"G Kadmon","year":"1990","journal-title":"J Cell Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1006\/cbir.1999.0457","article-title":"CD56 directly interacts in the process of NCAM-positive target cell-killing by NK cells","volume":"24","author":"S Takasaki","year":"2000","journal-title":"Cell Biol Int"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1128\/JVI.01120-10","article-title":"Natural suppression of human immunodeficiency virus type 1 replication is mediated by transitional memory CD8+ T cells","volume":"85","author":"MS Killian","year":"2011","journal-title":"J Virol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s10875-005-0358-3","article-title":"Not all tetramer binding CD8+ T cells can produce cytokines and chemokines involved in the effector functions of virus-specific CD8+ T lymphocytes in HIV-1 infected children","volume":"25","author":"D Scott-Algara","year":"2005","journal-title":"J Clin Immunol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.immuni.2008.10.010","article-title":"Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control","volume":"29","author":"SA Migueles","year":"2008","journal-title":"Immunity"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1189\/jlb.0312146","article-title":"CD56+ T cells inhibit HIV-1 infection of macrophages","volume":"92","author":"W Hou","year":"2012","journal-title":"J Leukoc Biol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1007\/BF01257243","article-title":"Highly sialylated N-CAM is expressed in adult mouse optic nerve and retina","volume":"19","author":"U Bartsch","year":"1990","journal-title":"J Neurocytol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0165-2478(98)00165-5","article-title":"Characterization of HIV-1-specific T-helper cells in acute and chronic infection","volume":"66","author":"ES Rosenberg","year":"1999","journal-title":"Immunol Lett"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"e60186","DOI":"10.1371\/journal.pone.0060186","article-title":"Re-evaluation of PD-1 expression by T cells as a marker for immune exhaustion during SIV infection","volume":"8","author":"JJ Hong","year":"2013","journal-title":"PLoS One"},{"key":"ref45","doi-asserted-by":"crossref","unstructured":"Finney CA, Ayi K, Wasmuth JD, Sheth PM, Kaul R, <etal>et al<\/etal>.. (2013) HIV Infection Deregulates Tim-3 Expression on Innate Cells; Combination Antiretroviral Therapy Results in Partial Restoration. J Acquir Immune Defic Syndr.","DOI":"10.1097\/QAI.0b013e318285cf13"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1182\/blood-2002-07-1957","article-title":"IL-15 enhances survival and function of HIV-specific CD8+ T cells","volume":"101","author":"YM Mueller","year":"2003","journal-title":"Blood"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1182\/blood.V85.10.2654.bloodjournal85102654","article-title":"Development of human T and natural killer cells","volume":"85","author":"H Spits","year":"1995","journal-title":"Blood"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1182\/blood-2007-03-082206","article-title":"Notch signaling induces cytoplasmic CD3 epsilon expression in human differentiating NK cells","volume":"110","author":"M De Smedt","year":"2007","journal-title":"Blood"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/1479-5876-10-94","article-title":"Effects of combined antiretroviral therapy on B- and T-cell release from production sites in long-term treated HIV-1+ patients","volume":"10","author":"E Quiros-Roldan","year":"2012","journal-title":"J Transl Med"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1468-1293.2004.00187.x","article-title":"Evidence of thymic reconstitution after highly active antiretroviral therapy in HIV-1 infection","volume":"5","author":"G Hardy","year":"2004","journal-title":"HIV Med"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0088884","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,15]],"date-time":"2020-08-15T07:46:38Z","timestamp":1597477598000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0088884"}},"subtitle":[],"editor":[{"given":"Derya","family":"Unutmaz","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2014,2,10]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2014,2,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0088884","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2,10]]}}}