{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T12:27:06Z","timestamp":1790944026344,"version":"4.1.0"},"reference-count":54,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite the frequency of HIV-specific CD8 T cells, most HIV-infected patients do not control viral replication without antiviral drugs. Although CD8 T cells are important in containing acute HIV and simian immunodeficiency virus (SIV) infection, CD8 T-cell functions are compromised in chronic infection. To investigate whether functional deficits are specific to HIV, the phenotypic and functional properties of HIV, Epstein-Barr virus (EBV), and cytomegalovirus (CMV)\u2013specific CD8 T cells, labeled with HLA A2.1 or B8 tetramers, were compared in 35 HIV-infected and 9 healthy donors. Cytotoxic T lymphocytes express the cytolytic molecules perforin and granzymes, and are thought to be CD45RA+CD27\u2212. Although most HIV- specific cells are antigen experienced and express granzyme A (median, 85%), few express high levels of perforin (median, 10%) or CD45RA (median, 14%) or have down-modulated CD27 (median, 12%). Perforin expression by HIV-specific cells is not significantly different from that of EBV- or CMV-specific cells in the same donors or in healthy donors. EBV- and CMV-specific cells, like HIV-specific cells, are often not cytotoxic when tested directly ex vivo. HIV-specific T-cell expression of other phenotypic markers is similar to that of EBV- and CMV-specific CD8 T cells in healthy donors. However, CMV-specific cells (and, to a lesser extent, EBV-specific cells) in HIV-infected donors are more likely to be CD27\u2212, CD45RA+, and GzmA+. These results suggest that the chance to eradicate an infection by T-cell\u2013mediated lysis may be undermined once an infection becomes chronic. Impaired antiviral cytotoxicity during chronic infection is not specific to HIV but likely represents the immune response to chronic antigenic exposure.<\/jats:p>","DOI":"10.1182\/blood-2002-03-0791","type":"journal-article","created":{"date-parts":[[2002,12,16]],"date-time":"2002-12-16T21:02:38Z","timestamp":1040072558000},"page":"226-235","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":143,"title":["Most antiviral CD8 T cells during chronic viral infection do not express high levels of perforin and are not directly cytotoxic"],"prefix":"10.1182","volume":"101","author":[{"given":"Dong","family":"Zhang","sequence":"first","affiliation":[{"name":"From the Center for Blood Research, Department of Pediatrics, and Department of Biostatistical Science\/Dana Farber Cancer Institute, Harvard Medical School, Boston, MA; and the Center for AIDS Research, University Hospitals of Cleveland, Case Western Reserve University, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Premlata","family":"Shankar","sequence":"additional","affiliation":[{"name":"From the Center for Blood Research, Department of Pediatrics, and Department of Biostatistical Science\/Dana Farber Cancer Institute, Harvard Medical School, Boston, MA; and the Center for AIDS Research, University Hospitals of Cleveland, Case Western Reserve University, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Xu","sequence":"additional","affiliation":[{"name":"From the Center for Blood Research, Department of Pediatrics, and Department of Biostatistical Science\/Dana Farber Cancer Institute, Harvard Medical School, Boston, MA; and the Center for AIDS Research, University Hospitals of Cleveland, Case Western Reserve University, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke","family":"Harnisch","sequence":"additional","affiliation":[{"name":"From the Center for Blood Research, Department of Pediatrics, and Department of Biostatistical Science\/Dana Farber Cancer Institute, Harvard Medical School, Boston, MA; and the Center for AIDS Research, University Hospitals of Cleveland, Case Western Reserve University, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Center for Blood Research, Department of Pediatrics, and Department of Biostatistical Science\/Dana Farber Cancer Institute, Harvard Medical School, Boston, MA; and the Center for AIDS Research, University Hospitals of Cleveland, Case Western Reserve University, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Lange","sequence":"additional","affiliation":[{"name":"From the Center for Blood Research, Department of Pediatrics, and Department of Biostatistical Science\/Dana Farber Cancer Institute, Harvard Medical School, Boston, MA; and the Center for AIDS Research, University Hospitals of Cleveland, Case Western Reserve University, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra J.","family":"Lee","sequence":"additional","affiliation":[{"name":"From the Center for Blood Research, Department of Pediatrics, and Department of Biostatistical Science\/Dana Farber Cancer Institute, Harvard Medical School, Boston, MA; and the Center for AIDS Research, University Hospitals of Cleveland, Case Western Reserve University, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hernan","family":"Valdez","sequence":"additional","affiliation":[{"name":"From the Center for Blood Research, Department of Pediatrics, and Department of Biostatistical Science\/Dana Farber Cancer Institute, Harvard Medical School, Boston, MA; and the Center for AIDS Research, University Hospitals of Cleveland, Case Western Reserve University, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Lederman","sequence":"additional","affiliation":[{"name":"From the Center for Blood Research, Department of Pediatrics, and Department of Biostatistical Science\/Dana Farber Cancer Institute, Harvard Medical School, Boston, MA; and the Center for AIDS Research, University Hospitals of Cleveland, Case Western Reserve University, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Lieberman","sequence":"additional","affiliation":[{"name":"From the Center for Blood Research, Department of Pediatrics, and Department of Biostatistical Science\/Dana Farber Cancer Institute, Harvard Medical School, Boston, MA; and the Center for AIDS Research, University Hospitals of Cleveland, Case Western Reserve University, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021300244661200_B1","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1126\/science.2431484","article-title":"CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication.","volume":"234","author":"Walker","year":"1986","journal-title":"Science."},{"key":"2020021300244661200_B2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/328345a0","article-title":"HIV-specific cytotoxic T lymphocytes in seropositive individuals.","volume":"328","author":"Walker","year":"1987","journal-title":"Nature."},{"key":"2020021300244661200_B3","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1126\/science.270.5243.1811","article-title":"Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells.","volume":"270","author":"Cocchi","year":"1995","journal-title":"Science."},{"key":"2020021300244661200_B4","doi-asserted-by":"crossref","first-page":"4650","DOI":"10.1128\/JVI.68.7.4650-4655.1994","article-title":"Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome.","volume":"68","author":"Koup","year":"1994","journal-title":"J Virol."},{"key":"2020021300244661200_B5","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nm0297-205","article-title":"Antiviral pressure exerted by HIV-1\u2013specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus.","volume":"3","author":"Borrow","year":"1997","journal-title":"Nat Med."},{"key":"2020021300244661200_B6","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1126\/science.283.5403.857","article-title":"Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes.","volume":"283","author":"Schmitz","year":"1999","journal-title":"Science."},{"key":"2020021300244661200_B7","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1084\/jem.189.6.991","article-title":"Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques.","volume":"189","author":"Jin","year":"1999","journal-title":"J Exp Med."},{"key":"2020021300244661200_B8","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1182\/blood.V98.6.1667","article-title":"Dressed to kill? a review of why antiviral CD8 T lymphocytes fail to prevent progressive immunodeficiency in HIV-1 infection.","volume":"98","author":"Lieberman","year":"2001","journal-title":"Blood."},{"key":"2020021300244661200_B9","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1182\/blood.V94.9.3084","article-title":"Viral-specific cytotoxic T lymphocytes lyse HIV-infected primary T lymphocytes by the granule exocytosis pathway.","volume":"94","author":"Shankar","year":"1999","journal-title":"Blood."},{"key":"2020021300244661200_B10","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1097\/00002030-199907300-00005","article-title":"Perforin is not co-expressed with granzyme A within cytotoxic granules in CD8 T lymphocytes present in lymphoid tissue during chronic HIV infection.","volume":"13","author":"Andersson","year":"1999","journal-title":"AIDS."},{"key":"2020021300244661200_B11","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1086\/340124","article-title":"Low levels of perforin expression in CD8+ T lymphocyte granules in lymphoid tissue during acute human immunodeficiency virus type 1 infection.","volume":"185","author":"Andersson","year":"2002","journal-title":"J Infect Dis."},{"key":"2020021300244661200_B12","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1182\/blood.V98.1.156","article-title":"CD8 T cells specific for human immunodeficiency virus, Epstein-Barr virus, and cytomegalovirus lack molecules for homing to lymphoid sites of infection.","volume":"98","author":"Chen","year":"2001","journal-title":"Blood."},{"key":"2020021300244661200_B13","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1084\/jem.192.1.63","article-title":"HIVspecific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function.","volume":"192","author":"Appay","year":"2000","journal-title":"J Exp Med."},{"key":"2020021300244661200_B14","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1084\/jem.186.9.1407","article-title":"Phenotypic and functional separation of memory and effector human CD8+ T cells.","volume":"186","author":"Hamann","year":"1997","journal-title":"J Exp Med."},{"key":"2020021300244661200_B15","doi-asserted-by":"crossref","first-page":"181","DOI":"10.4049\/jimmunol.167.1.181","article-title":"Functional heterogeneity of cytokines and cytolytic effector molecules in human CD8+ T lymphocytes.","volume":"167","author":"Sandberg","year":"2001","journal-title":"J Immunol."},{"key":"2020021300244661200_B16","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.4049\/jimmunol.167.4.2019","article-title":"EBV-specific CD8+ T cell memory: relationships between epitope specificity, cell phenotype, and immediate effector function.","volume":"167","author":"Hislop","year":"2001","journal-title":"J Immunol."},{"key":"2020021300244661200_B17","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nm0402-379","article-title":"Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections.","volume":"8","author":"Appay","year":"2002","journal-title":"Nat Med."},{"key":"2020021300244661200_B18","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/S0952-7915(02)00366-7","article-title":"Avoiding the kiss of death: how HIV and other chronic viruses survive.","volume":"14","author":"Lieberman","year":"2002","journal-title":"Curr Opin Immunol."},{"key":"2020021300244661200_B19","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1182\/blood.V96.9.3094","article-title":"Impaired function of circulating HIV-specific CD8(+) T cells in chronic human immunodeficiency virus infection.","volume":"96","author":"Shankar","year":"2000","journal-title":"Blood."},{"key":"2020021300244661200_B20","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1182\/blood.V91.2.585","article-title":"Circulating CD8 T lymphocytes in human immunodeficiency virus-infected individuals have impaired function and downmodulate CD3 zeta, the signaling chain of the T-cell receptor complex.","volume":"91","author":"Trimble","year":"1998","journal-title":"Blood."},{"key":"2020021300244661200_B21","doi-asserted-by":"crossref","first-page":"6133","DOI":"10.4049\/jimmunol.165.11.6133","article-title":"The role of CD4(+) T cell help and CD40 ligand in the in vitro expansion of HIV-1-specific memory cytotoxic CD8(+) T cell responses.","volume":"165","author":"Ostrowski","year":"2000","journal-title":"J Immunol."},{"key":"2020021300244661200_B22","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1126\/science.274.5284.94","article-title":"Phenotypic analysis of antigen-specific T lymphocytes.","volume":"274","author":"Altman","year":"1996","journal-title":"Science."},{"key":"2020021300244661200_B23","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.4049\/jimmunol.147.5.1512","article-title":"HIV-1 gag-specific cytotoxic T lymphocytes recognize multiple highly conserved epitopes: fine specificity of the gag-specific response defined by using unstimulated peripheral blood mononuclear cells and cloned effector cells.","volume":"147","author":"Johnson","year":"1991","journal-title":"J Immunol."},{"key":"2020021300244661200_B24","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1126\/science.279.5359.2103","article-title":"Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA.","volume":"279","author":"Ogg","year":"1998","journal-title":"Science."},{"key":"2020021300244661200_B25","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1126\/science.2451288","article-title":"HIV-1 reverse transcriptase is a target for cytotoxic T lymphocytes in infected individuals.","volume":"240","author":"Walker","year":"1988","journal-title":"Science."},{"key":"2020021300244661200_B26","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1097\/00042560-199810010-00002","article-title":"Effective lysis of HIV-1-infected primary CD4+ T cells by a cytotoxic T-lymphocyte clone directed against a novel A2-restricted reverse-transcriptase epitope.","volume":"19","author":"Shankar","year":"1998","journal-title":"J Acquir Immune Defic Syndr Hum Retrovirol."},{"key":"2020021300244661200_B27","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0165-2478(96)02574-6","article-title":"Three regions of HIV-1 gp160 contain clusters of immunodominant CTL epitopes.","volume":"52","author":"Shankar","year":"1996","journal-title":"Immunol Lett."},{"key":"2020021300244661200_B28","doi-asserted-by":"crossref","first-page":"7569","DOI":"10.1128\/JVI.70.11.7569-7579.1996","article-title":"The human cytotoxic T-lymphocyte (CTL) response to cytomegalovirus is dominated by structural protein pp65: frequency, specificity, and T-cell receptor usage of pp65-specific CTL.","volume":"70","author":"Wills","year":"1996","journal-title":"J Virol."},{"key":"2020021300244661200_B29","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1097\/00007890-200006150-00005","article-title":"Characterization of CMVpp65-specific CD8+ T lymphocytes using MHC tetramers in kidney transplant patients and healthy participants.","volume":"69","author":"Engstrand","year":"2000","journal-title":"Transplantation."},{"key":"2020021300244661200_B30","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1097\/00007890-200006150-00006","article-title":"Direct visualization and quantitation of cytomegalovirus-specific CD8+ cytotoxic T-lymphocytes in liver transplant patients.","volume":"69","author":"Singhal","year":"2000","journal-title":"Transplantation."},{"key":"2020021300244661200_B31","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1084\/jem.185.9.1605","article-title":"Immediate early and early lytic cycle proteins are frequent targets of the Epstein-Barr virus-induced cytotoxic T cell response.","volume":"185","author":"Steven","year":"1997","journal-title":"J Exp Med."},{"key":"2020021300244661200_B32","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1084\/jem.187.9.1395","article-title":"Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus in vivo.","volume":"187","author":"Callan","year":"1998","journal-title":"J Exp Med."},{"key":"2020021300244661200_B33","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1089\/aid.1995.11.257","article-title":"Ex vivo expansion of HIV type 1-specific cytolytic T cells from HIV type 1-seropositive subjects.","volume":"11","author":"Lieberman","year":"1995","journal-title":"AIDS Res Hum Retroviruses."},{"key":"2020021300244661200_B34","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/35065118","article-title":"Skewed maturation of memory HIV-specific CD8 T lymphocytes.","volume":"410","author":"Champagne","year":"2001","journal-title":"Nature."},{"key":"2020021300244661200_B35","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1128\/JVI.75.5.2458-2461.2001","article-title":"Functional impairment of simian immunodeficiency virus-specific CD8+ T cells during the chronic phase of infection.","volume":"75","author":"Vogel","year":"2001","journal-title":"J Virol."},{"key":"2020021300244661200_B36","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1084\/jem.187.5.763","article-title":"Viral and bacterial infections interfere with peripheral tolerance induction and activate CD8+ T cells to cause immunopathology.","volume":"187","author":"Ehl","year":"1998","journal-title":"J Exp Med."},{"key":"2020021300244661200_B37","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":"Oxenius","year":"1998","journal-title":"Eur J Immunol."},{"key":"2020021300244661200_B38","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.4049\/jimmunol.168.7.3477","article-title":"Reduced functional capacity of CD8(+) T cells expanded by post-exposure vaccination of gamma-herpesvirus-infected CD4-deficient mice.","volume":"168","author":"Liu","year":"2002","journal-title":"J Immunol."},{"key":"2020021300244661200_B39","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1097\/00002030-199905280-00004","article-title":"Expansion of CD57 and CD62L-CD45RA+ CD8 T lymphocytes correlates with reduced viral plasma RNA after primary HIV infection.","volume":"13","author":"Lieberman","year":"1999","journal-title":"AIDS."},{"key":"2020021300244661200_B40","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/43454","article-title":"Rapid on\/off cycling of cytokine production by virus-specific CD8+ T cells.","volume":"401","author":"Slifka","year":"1999","journal-title":"Nature."},{"key":"2020021300244661200_B41","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.4049\/jimmunol.143.11.3440","article-title":"Perforin mRNA in primary peritoneal exudate cytotoxic T lymphocytes.","volume":"143","author":"Nagler-Anderson","year":"1989","journal-title":"J Immunol."},{"key":"2020021300244661200_B42","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1172\/JCI118915","article-title":"HIV infection-induced posttranslational modification of T cell signaling molecules associated with disease progression.","volume":"98","author":"Stefanova","year":"1996","journal-title":"J Clin Invest."},{"key":"2020021300244661200_B43","doi-asserted-by":"crossref","first-page":"9983","DOI":"10.1128\/JVI.75.20.9983-9985.2001","article-title":"Differential expression of interleukin-2 and gamma interferon in human immunodeficiency virus disease.","volume":"75","author":"Sieg","year":"2001","journal-title":"J Virol."},{"key":"2020021300244661200_B44","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1084\/jem.190.9.1297","article-title":"Interleukin 2 receptor signaling regulates the perforin gene through signal transducer and activator of transcription (Stat)5 activation of two enhancers.","volume":"190","author":"Zhang","year":"1999","journal-title":"J Exp Med."},{"key":"2020021300244661200_B45","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1182\/blood.V96.3.1021","article-title":"CD3zeta and CD28 down-modulation on CD8 T cells during viral infection.","volume":"96","author":"Trimble","year":"2000","journal-title":"Blood."},{"key":"2020021300244661200_B46","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":"Trimble","year":"2000","journal-title":"J Virol."},{"key":"2020021300244661200_B47","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1126\/science.278.5342.1447","article-title":"Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia.","volume":"278","author":"Rosenberg","year":"1997","journal-title":"Science."},{"key":"2020021300244661200_B48","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1084\/jem.188.12.2205","article-title":"Viral immune evasion due to persistence of activated T cells without effector function.","volume":"188","author":"Zajac","year":"1998","journal-title":"J Exp Med."},{"key":"2020021300244661200_B49","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1084\/jem.188.12.2199","article-title":"The critical need for CD4 help in maintaining effective cytotoxic T lymphocyte responses.","volume":"188","author":"Kalams","year":"1998","journal-title":"J Exp Med."},{"key":"2020021300244661200_B50","doi-asserted-by":"crossref","first-page":"6715","DOI":"10.1128\/JVI.73.8.6715-6720.1999","article-title":"Association between virus-specific cytotoxic T-lymphocyte and helper responses in human immunodeficiency virus type 1 infection.","volume":"73","author":"Kalams","year":"1999","journal-title":"J Virol."},{"key":"2020021300244661200_B51","doi-asserted-by":"crossref","first-page":"4884","DOI":"10.1128\/JVI.70.8.4884-4894.1996","article-title":"Frequency of multiple Epstein-Barr virus infections in T-cell\u2013immunocompromised individuals.","volume":"70","author":"Yao","year":"1996","journal-title":"J Virol."},{"key":"2020021300244661200_B52","first-page":"293","article-title":"Diagnostic significance and clinical impact of quantitative assays for diagnosis of human cytomegalovirus infection\/disease in immunocompromised patients.","volume":"21","author":"Gerna","year":"1998","journal-title":"New Microbiol."},{"key":"2020021300244661200_B53","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/354453a0","article-title":"Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition.","volume":"354","author":"Phillips","year":"1991","journal-title":"Nature."},{"key":"2020021300244661200_B54","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/34929","article-title":"HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes.","volume":"391","author":"Collins","year":"1998","journal-title":"Nature."}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/101\/1\/226\/1686724\/h80103000226.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/101\/1\/226\/1686724\/h80103000226.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T20:10:19Z","timestamp":1682280619000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/101\/1\/226\/88962\/Most-antiviral-CD8-T-cells-during-chronic-viral"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1,1]]},"references-count":54,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,1,1]]}},"URL":"https:\/\/doi.org\/10.1182\/blood-2002-03-0791","relation":{},"ISSN":["1528-0020","0006-4971"],"issn-type":[{"value":"1528-0020","type":"electronic"},{"value":"0006-4971","type":"print"}],"subject":[],"published":{"date-parts":[[2003,1,1]]}}}