{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T16:59:28Z","timestamp":1788195568246,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,26]],"date-time":"2020-01-26T00:00:00Z","timestamp":1579996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Cytotoxic activity mediated by CD8<jats:sup>+<\/jats:sup> T cells is the main signature of the immunopathogenesis of cutaneous leishmaniasis (CL). Here, we performed a broad evaluation of natural killer (NK) cell phenotypic and functional features during cutaneous leishmaniasis. We demonstrate for the first time that CL patients present the accumulation of circulating NK cells with multiple features of replicative senescence including low proliferative capacity and shorter telomeres, elevated expression of CD57, KLRG1 but diminished CD27 stimulatory receptor expression. Moreover, they exhibited higher cytotoxic and inflammatory potential than age\u2010matched controls. The accumulation of circulating senescent NK cells (CD56<jats:sup>dim<\/jats:sup>\u00a0CD57<jats:sup>bright<\/jats:sup>) correlated positively with skin lesion size in the same patients, suggesting that they, like circulating senescent CD8<jats:sup>+<\/jats:sup> T cells, may contribute to the immunopathology of CL. However, this senescent population had lower cutaneous lymphocyte antigen expression and so had diminished skin\u2010homing potential compared with total or senescent CD8<jats:sup>+<\/jats:sup> T cells. This was confirmed in CL skin lesions where we found a predominance of CD8<jats:sup>+<\/jats:sup> T cells (both senescent and non\u2010senescent) that correlated with the severity of the disease. Although there was also a correlation between the proportions of senescent NK cells (CD56<jats:sup>+<\/jats:sup>\u00a0CD57<jats:sup>+<\/jats:sup>) in the skin and lesion size, this was less evident. Collectively our results demonstrate first\u2010hand that senescent cytotoxic cells may mediate skin pathology during human cutaneous leishmaniasis. However, as senescent cytotoxic CD8<jats:sup>+<\/jats:sup> T cells predominate in the skin lesions, they may have a greater role than NK cells in mediating the non\u2010specific skin damage in CL.<\/jats:p>","DOI":"10.1111\/imm.13173","type":"journal-article","created":{"date-parts":[[2020,1,11]],"date-time":"2020-01-11T01:55:38Z","timestamp":1578707738000},"page":"429-440","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Compartmentalized cytotoxic immune response leads to distinct pathogenic roles of natural killer and senescent CD8<sup>+<\/sup> T cells in human cutaneous leishmaniasis"],"prefix":"10.1111","volume":"159","author":[{"given":"Luciana Polaco","family":"Covre","sequence":"first","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas Universidade Federal do Esp\u00edrito Santo Esp\u00edrito Santo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver Patrick","family":"Devine","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renan","family":"Garcia de Moura","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas Universidade Federal do Esp\u00edrito Santo Esp\u00edrito Santo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milica","family":"Vukmanovic\u2010Stejic","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reynaldo","family":"Dietze","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas Universidade Federal do Esp\u00edrito Santo Esp\u00edrito Santo Brazil"},{"name":"Global Health &amp; Tropical Medicine Instituto de Higiene e Medicina Tropical Universidade Nova de Lisboa Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Ribeiro\u2010Rodrigues","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas Universidade Federal do Esp\u00edrito Santo Esp\u00edrito Santo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert Leonel de Matos","family":"Guedes","sequence":"additional","affiliation":[{"name":"Instituto de Biof\u00edsica Carlos Chagas Filho Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"},{"name":"Instituto Oswaldo Cruz Funda\u00e7\u00e3o Oswaldo Cruz Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Lubiana Zanotti","sequence":"additional","affiliation":[{"name":"Secretaria Estadual de Sa\u00fade Esp\u00edrito Santo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aloisio","family":"Falqueto","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Social Universidade Federal do Esp\u00edrito Santo Esp\u00edrito Santo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne N.","family":"Akbar","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0663-0981","authenticated-orcid":false,"given":"Daniel Claudio Oliveira","family":"Gomes","sequence":"additional","affiliation":[{"name":"N\u00facleo de Doen\u00e7as Infecciosas Universidade Federal do Esp\u00edrito Santo Esp\u00edrito Santo Brazil"},{"name":"N\u00facleo de Biotecnologia Universidade Federal do Esp\u00edrito Santo Esp\u00edrito Santo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,26]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Investing to overcome the global impact of neglected tropical diseases: third WHO report on neglected diseases 2015","author":"WHO","year":"2015"},{"key":"e_1_2_8_3_1","first-page":"432","article-title":"Recruitment of CD8+ T cell expressing granzyme A is associated with lesion progression in human cutaneous leishmaniasis","volume":"3","author":"Faria DR","year":"2010","journal-title":"Parasite Immunol"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006196"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003504"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.4"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.305"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03001"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-282301"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.6.2698-2704.1998"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12312"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2009.81.378"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.61.8.3565-3569.1993"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-017-2152-2"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz538"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"4467","DOI":"10.4049\/jimmunol.159.9.4467","article-title":"Parasite\u2010driven in vitro human lymphocyte cytotoxicity against autologous infected macrophages from mucosal leishmaniasis","volume":"9","author":"Brodskyn CI","year":"1997","journal-title":"J Immunol"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2014.01.007"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2008.08.007"},{"key":"e_1_2_8_19_1","first-page":"499","article-title":"Signatures of human NK cell development and terminal differentiation","volume":"30","author":"Luetke\u2010Eversloh M","year":"2013","journal-title":"Front Immunol"},{"key":"e_1_2_8_20_1","first-page":"445","article-title":"Convergence of innate and adaptive immunity during human aging","volume":"4","author":"Pereira BI","year":"2016","journal-title":"Front Immunol"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2594"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00422"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600590"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0047-6374(00)00199-8"},{"key":"e_1_2_8_25_1","first-page":"647","article-title":"Circulating CLA+ T cell subsets inversely correlate with disease severity and extension in acute psoriasis but not in chronic plaque psoriasis","volume":"18","author":"Ferran M","year":"2008","journal-title":"Eur J Dermatol"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215537"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2009.03970.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"466","DOI":"10.4049\/jimmunol.163.1.466","article-title":"Skin homing (cutaneous lymphocyte\u2010associated antigen\u2010positive) CD8+ T cells respond to superantigen and contribute to eosinophilia and IgE production in atopic dermatitis","volume":"163","author":"Akdis M","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2006.02528.x"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.62.3.837-842.1994"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12925"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10335-5"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003970"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fimm.13173","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.13173","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imm.13173","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.13173","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T14:58:31Z","timestamp":1694098711000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.13173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,26]]},"references-count":32,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.1111\/imm.13173"],"URL":"https:\/\/doi.org\/10.1111\/imm.13173","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,26]]},"assertion":[{"value":"2019-10-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}