Increased natural killer cell activity in viremic HIV-1 infection
NK cells are a subset of granular lymphocytes that are critical in the innate immune response to infection. These cells are capable of killing infected cells and secreting integral cytokines and chemokines. The role that this subset of cytolytic cells plays in HIV infection is not well understood. I...
Saved in:
| Published in: | The Journal of immunology (1950) Vol. 173; no. 8; p. 5305 |
|---|---|
| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
15.10.2004
|
| Subjects: | |
| ISSN: | 0022-1767 |
| Online Access: | Get more information |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | NK cells are a subset of granular lymphocytes that are critical in the innate immune response to infection. These cells are capable of killing infected cells and secreting integral cytokines and chemokines. The role that this subset of cytolytic cells plays in HIV infection is not well understood. In this study, we dissected the function of NK cells in viremic and aviremic HIV-1-infected subjects, as well as HIV-1-negative control individuals. Despite reduced NK cell numbers in subjects with ongoing viral replication, these cells were significantly more active in secreting both IFN-gamma and TNF-alpha than NK cells from aviremic subjects or HIV-1-negative controls. In addition, NK cells in subjects with detectable viral loads expressed significantly higher levels of CD107a, a marker of lysosomal granule exocytosis. The expression of CD107a correlated with NK cell-mediated cytokine secretion and cytolytic activity as well as with the level of viral replication, suggesting that CD107a represents a good marker for the functional activity of NK cells. Finally, killer Ig-related receptor+ NK cells were stable or elevated in viremic subjects, while the numbers of CD3-/CD56+/CD94+ and CD3-/CD56+/CD161+ NK cells were reduced. Taken together, these data demonstrate that viremic HIV-1 infection is associated with a reduction in NK cell numbers and a perturbation of NK cell subsets, but increased overall NK cell activity. |
|---|---|
| AbstractList | NK cells are a subset of granular lymphocytes that are critical in the innate immune response to infection. These cells are capable of killing infected cells and secreting integral cytokines and chemokines. The role that this subset of cytolytic cells plays in HIV infection is not well understood. In this study, we dissected the function of NK cells in viremic and aviremic HIV-1-infected subjects, as well as HIV-1-negative control individuals. Despite reduced NK cell numbers in subjects with ongoing viral replication, these cells were significantly more active in secreting both IFN-gamma and TNF-alpha than NK cells from aviremic subjects or HIV-1-negative controls. In addition, NK cells in subjects with detectable viral loads expressed significantly higher levels of CD107a, a marker of lysosomal granule exocytosis. The expression of CD107a correlated with NK cell-mediated cytokine secretion and cytolytic activity as well as with the level of viral replication, suggesting that CD107a represents a good marker for the functional activity of NK cells. Finally, killer Ig-related receptor+ NK cells were stable or elevated in viremic subjects, while the numbers of CD3-/CD56+/CD94+ and CD3-/CD56+/CD161+ NK cells were reduced. Taken together, these data demonstrate that viremic HIV-1 infection is associated with a reduction in NK cell numbers and a perturbation of NK cell subsets, but increased overall NK cell activity. NK cells are a subset of granular lymphocytes that are critical in the innate immune response to infection. These cells are capable of killing infected cells and secreting integral cytokines and chemokines. The role that this subset of cytolytic cells plays in HIV infection is not well understood. In this study, we dissected the function of NK cells in viremic and aviremic HIV-1-infected subjects, as well as HIV-1-negative control individuals. Despite reduced NK cell numbers in subjects with ongoing viral replication, these cells were significantly more active in secreting both IFN-gamma and TNF-alpha than NK cells from aviremic subjects or HIV-1-negative controls. In addition, NK cells in subjects with detectable viral loads expressed significantly higher levels of CD107a, a marker of lysosomal granule exocytosis. The expression of CD107a correlated with NK cell-mediated cytokine secretion and cytolytic activity as well as with the level of viral replication, suggesting that CD107a represents a good marker for the functional activity of NK cells. Finally, killer Ig-related receptor+ NK cells were stable or elevated in viremic subjects, while the numbers of CD3-/CD56+/CD94+ and CD3-/CD56+/CD161+ NK cells were reduced. Taken together, these data demonstrate that viremic HIV-1 infection is associated with a reduction in NK cell numbers and a perturbation of NK cell subsets, but increased overall NK cell activity.NK cells are a subset of granular lymphocytes that are critical in the innate immune response to infection. These cells are capable of killing infected cells and secreting integral cytokines and chemokines. The role that this subset of cytolytic cells plays in HIV infection is not well understood. In this study, we dissected the function of NK cells in viremic and aviremic HIV-1-infected subjects, as well as HIV-1-negative control individuals. Despite reduced NK cell numbers in subjects with ongoing viral replication, these cells were significantly more active in secreting both IFN-gamma and TNF-alpha than NK cells from aviremic subjects or HIV-1-negative controls. In addition, NK cells in subjects with detectable viral loads expressed significantly higher levels of CD107a, a marker of lysosomal granule exocytosis. The expression of CD107a correlated with NK cell-mediated cytokine secretion and cytolytic activity as well as with the level of viral replication, suggesting that CD107a represents a good marker for the functional activity of NK cells. Finally, killer Ig-related receptor+ NK cells were stable or elevated in viremic subjects, while the numbers of CD3-/CD56+/CD94+ and CD3-/CD56+/CD161+ NK cells were reduced. Taken together, these data demonstrate that viremic HIV-1 infection is associated with a reduction in NK cell numbers and a perturbation of NK cell subsets, but increased overall NK cell activity. |
| Author | Zaunders, John Alter, Galit Malenfant, Jessica M Delabre, Rosemary M Yu, Xu G Lichterfeld, Mathias Burgett, Nicole C Altfeld, Marcus |
| Author_xml | – sequence: 1 givenname: Galit surname: Alter fullname: Alter, Galit organization: Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston 02129, USA – sequence: 2 givenname: Jessica M surname: Malenfant fullname: Malenfant, Jessica M – sequence: 3 givenname: Rosemary M surname: Delabre fullname: Delabre, Rosemary M – sequence: 4 givenname: Nicole C surname: Burgett fullname: Burgett, Nicole C – sequence: 5 givenname: Xu G surname: Yu fullname: Yu, Xu G – sequence: 6 givenname: Mathias surname: Lichterfeld fullname: Lichterfeld, Mathias – sequence: 7 givenname: John surname: Zaunders fullname: Zaunders, John – sequence: 8 givenname: Marcus surname: Altfeld fullname: Altfeld, Marcus |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/15470077$$D View this record in MEDLINE/PubMed |
| BookMark | eNo1j01LxDAYhHNYcT_0FwjSk7fWN2k-muOyqLuw4EW9lmz6FrKm6Zq0C_vvraingZmHYWZJZqEPSMgdhYID149H13Vj6H1BVVlUhShBzMgCgLGcKqnmZJnSEQAkMH5N5lRwBaDUgqx3wUY0CZssmGGMxmefznuMmUXvM2MHd3bDJXMhO7uInbPZdveR08locQr7cEOuWuMT3v7pirw_P71ttvn-9WW3We9zy5UYcl2iAkrbhmlLWVuiBKOtONjKWNk0XGhqG5zYgy55VWpQ3FqOWphGaF4hW5GH395T7L9GTEPdufQz0gTsx1RLqbnUDCbw_g8cDx029Sm6zsRL_X-afQMgXVqG |
| CitedBy_id | crossref_primary_10_1186_s12879_024_09772_5 crossref_primary_10_1182_blood_2005_03_1100 crossref_primary_10_1089_vim_2011_0025 crossref_primary_10_1146_annurev_immunol_24_021605_090605 crossref_primary_10_1189_jlb_0610371 crossref_primary_10_1016_j_clim_2009_03_518 crossref_primary_10_1016_j_exphem_2009_07_009 crossref_primary_10_1097_QAD_0b013e328012b85f crossref_primary_10_1128_CVI_00042_06 crossref_primary_10_1128_JVI_01675_09 crossref_primary_10_2217_bmm_11_15 crossref_primary_10_1586_erv_10_49 crossref_primary_10_1111_j_1398_9995_2009_02180_x crossref_primary_10_1371_journal_pone_0103209 crossref_primary_10_1007_s10875_013_9930_1 crossref_primary_10_1016_j_imlet_2007_01_006 crossref_primary_10_1038_sj_leu_2403693 crossref_primary_10_1097_QAD_0000000000002743 crossref_primary_10_3390_cells13060530 crossref_primary_10_1016_j_tim_2012_09_001 crossref_primary_10_1097_QAI_0b013e3180dc9909 crossref_primary_10_1016_j_vaccine_2008_07_055 crossref_primary_10_1038_s41467_023_42435_8 crossref_primary_10_1097_01_cji_0000165357_11548_6d crossref_primary_10_1111_imr_12065 crossref_primary_10_3389_fimmu_2023_1131379 crossref_primary_10_1186_1743_422X_10_33 crossref_primary_10_1086_524141 crossref_primary_10_1097_CJI_0b013e318197b1b2 crossref_primary_10_3389_fimmu_2017_01496 crossref_primary_10_4049_jimmunol_0803954 crossref_primary_10_1007_s00281_016_0578_9 crossref_primary_10_1016_j_jhep_2011_06_017 crossref_primary_10_2217_hiv_10_28 crossref_primary_10_4049_jimmunol_179_4_2642 crossref_primary_10_1097_QAD_0b013e3283089367 crossref_primary_10_3389_fimmu_2016_00340 crossref_primary_10_1155_2016_2085871 crossref_primary_10_1016_j_jhep_2010_05_013 crossref_primary_10_1089_aid_2018_0243 crossref_primary_10_1097_QAD_0b013e3283367836 crossref_primary_10_1002_hep_21993 crossref_primary_10_1128_JVI_00753_09 crossref_primary_10_1038_ki_2013_59 crossref_primary_10_3389_fimmu_2018_00486 crossref_primary_10_1097_01_aids_0000191229_52385_5f crossref_primary_10_1111_j_1399_0039_2012_01843_x crossref_primary_10_1016_j_humimm_2017_01_004 crossref_primary_10_3389_fimmu_2022_842831 crossref_primary_10_1371_journal_pone_0242448 crossref_primary_10_1089_aid_2009_0176 crossref_primary_10_1128_JVI_01979_07 crossref_primary_10_1111_j_1365_2567_2009_03170_x crossref_primary_10_1186_s12981_015_0080_9 crossref_primary_10_1038_ki_2013_148 crossref_primary_10_1097_01_aids_0000237371_31315_48 crossref_primary_10_1016_j_conctc_2021_100866 crossref_primary_10_1038_sj_cr_7290301 crossref_primary_10_1189_jlb_5A1016_444R crossref_primary_10_1097_QAD_0000000000002721 crossref_primary_10_1016_j_coi_2006_05_002 crossref_primary_10_1182_blood_2006_08_040238 crossref_primary_10_1093_cid_ciab139 crossref_primary_10_3390_microorganisms11071637 crossref_primary_10_1016_j_jneuroim_2023_578067 crossref_primary_10_1089_vim_2007_0044 crossref_primary_10_1186_s12865_024_00615_1 crossref_primary_10_1111_j_1365_2567_2007_02657_x crossref_primary_10_1038_sj_leu_2403908 crossref_primary_10_4049_jimmunol_179_5_3362 crossref_primary_10_1189_jlb_0913514 crossref_primary_10_1016_j_clim_2007_05_016 crossref_primary_10_1371_journal_ppat_1000747 crossref_primary_10_1128_JVI_79_19_12365_12374_2005 crossref_primary_10_1182_blood_2011_12_395186 crossref_primary_10_1189_jlb_0907649 crossref_primary_10_1016_j_clim_2008_12_012 crossref_primary_10_1097_QAD_0000000000002976 crossref_primary_10_1016_j_cellimm_2004_12_004 crossref_primary_10_1080_08820139_2017_1402925 crossref_primary_10_1016_j_jaci_2018_11_052 crossref_primary_10_1038_sj_leu_2403704 |
| ContentType | Journal Article |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.4049/jimmunol.173.8.5305 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Medicine Biology |
| ExternalDocumentID | 15470077 |
| Genre | Research Support, U.S. Gov't, P.H.S Journal Article |
| GroupedDBID | --- -~X .55 .GJ 0R~ 18M 2WC 34G 39C 3O- 53G 5GY 5RE 5VS 5WD 79B 85S AARDX ABCQX ABDFA ABDPE ABEFU ABEJV ABGNP ABJNI ABOCM ABPPZ ABXVV ACGFO ACGFS ACIWK ACNCT ACPRK ADBBV ADIPN ADNWM ADXHL AENEX AETEA AFFNX AFHIN AFOSN AFRAH AGORE AHMMS AHWXS AI. AIZAD ALMA_UNASSIGNED_HOLDINGS ARBBW BAWUL BCRHZ BTFSW CGR CUY CVF D0L DIK DU5 E3Z EBS ECM EIF EJD F5P GX1 IH2 J5H K-O KQ8 L7B MVM NEJ NPM OCZFY OK1 OWPYF P0W P2P PQQKQ R.V RHI ROX RZQ SJN SKT TR2 TWZ VH1 W8F WH7 WOQ X7M XJT XSW XTH YHG ZE2 ZGI ZXP 7X8 KOP |
| ID | FETCH-LOGICAL-c475t-93e7011fd29c12f3e60a9c5bc8ac6dd4591cdec47b934839074cc4e95ad5948e2 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 93 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000224392200063&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 0022-1767 |
| IngestDate | Thu Oct 02 10:47:08 EDT 2025 Tue Aug 05 11:40:13 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 8 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c475t-93e7011fd29c12f3e60a9c5bc8ac6dd4591cdec47b934839074cc4e95ad5948e2 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | https://journals.aai.org/jimmunol/article-pdf/173/8/5305/1191075/5305.pdf |
| PMID | 15470077 |
| PQID | 66946920 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_66946920 pubmed_primary_15470077 |
| PublicationCentury | 2000 |
| PublicationDate | 2004-Oct-15 20041015 |
| PublicationDateYYYYMMDD | 2004-10-15 |
| PublicationDate_xml | – month: 10 year: 2004 text: 2004-Oct-15 day: 15 |
| PublicationDecade | 2000 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | The Journal of immunology (1950) |
| PublicationTitleAlternate | J Immunol |
| PublicationYear | 2004 |
| SSID | ssj0006024 |
| Score | 2.1432035 |
| Snippet | NK cells are a subset of granular lymphocytes that are critical in the innate immune response to infection. These cells are capable of killing infected cells... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 5305 |
| SubjectTerms | Acquired Immunodeficiency Syndrome - drug therapy Acquired Immunodeficiency Syndrome - immunology Adult Antigens, CD - analysis Antiretroviral Therapy, Highly Active CD3 Complex - analysis CD56 Antigen - analysis Female HIV-1 Humans Interferon-gamma - biosynthesis Killer Cells, Natural - immunology Lysosomal Membrane Proteins Lysosomal-Associated Membrane Protein 1 Male Middle Aged Tumor Necrosis Factor-alpha - biosynthesis Viremia - immunology |
| Title | Increased natural killer cell activity in viremic HIV-1 infection |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/15470077 https://www.proquest.com/docview/66946920 |
| Volume | 173 |
| WOSCitedRecordID | wos000224392200063&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS8QwEB7UVfHi-7E-c_CatW3eIIiIoqCLB5W9LW2SQn10V3dd8N87abd4Eg9ecmpKGCaTL5mZ7wM4TrXLtVcZzbXMKNdC0gxPKcoli62K04xXGdOnW9Xt6l7P3M_AadMLE8oqm5hYBWo3sOGN_ERKgze5JDobvtOgGRVyq1MBjVloMQQyoaBL9X64wmWU8IYrPFZS1ZxDHCHxyXMRmi8Gr51YsY7uCBaJ3xFmddJcrfxvjauwPEWY5Lx2iTWY8eU6LNSak1_rsHg3zaZvwDkGh1CT7h2p-D1x1kvVGkjCcz4JLQ9BWYIUJZlgZHwrLLm-eaIxaSq4yk14vLp8uLimU0kFarkSY2qYV7ijc5cYGyc58zJKjRWZ1amVznFhYus8fpsZxhE7IcCwlnsjUhd4XXyyBXPloPQ7QBKnlbO59QiRuNcmY8Ip5RzDH6Y-k204aozUR5cNC09LP_gc9RsztWG7tnN_WDNr9BHPqUAwtPvn3D1YqikXIxqLfWjluFn9AczbybgYfRxWnoBj9_7uG5rBvfE |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Increased+natural+killer+cell+activity+in+viremic+HIV-1+infection&rft.jtitle=The+Journal+of+immunology+%281950%29&rft.au=Alter%2C+Galit&rft.au=Malenfant%2C+Jessica+M&rft.au=Delabre%2C+Rosemary+M&rft.au=Burgett%2C+Nicole+C&rft.date=2004-10-15&rft.issn=0022-1767&rft.volume=173&rft.issue=8&rft.spage=5305&rft_id=info:doi/10.4049%2Fjimmunol.173.8.5305&rft_id=info%3Apmid%2F15470077&rft_id=info%3Apmid%2F15470077&rft.externalDocID=15470077 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0022-1767&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0022-1767&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0022-1767&client=summon |