{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:13:20Z","timestamp":1789913600916,"version":"4.0.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T00:00:00Z","timestamp":1542067200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"DOI":"10.3389\/fcimb.2018.00397","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T13:18:48Z","timestamp":1542115128000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Immunity Against Leishmania major Infection: Parasite-Specific Granzyme B Induction as a Correlate of Protection"],"prefix":"10.3389","volume":"8","author":[{"given":"Thouraya","family":"Boussoffara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadok","family":"Chelif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melika","family":"Ben Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mourad","family":"Mokni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afif","family":"Ben Salah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koussay","family":"Dellagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hechmi","family":"Louzir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,11,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/S0264-410X(02)00458-9","article-title":"The role of BCG in human immune responses induced by multiple injections of autoclaved Leishmania major as a candidate vaccine against leishmaniasis","volume":"2","author":"Alimohammadian","year":"2002","journal-title":"Vaccine"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1016\/j.vaccine.2003.06.002","article-title":"Safety, immunogenicity, and efficacy of an autoclaved Leishmania amazonensis vaccine plus BCG adjuvant against New World cutaneous leishmaniasis","volume":"22","author":"Armijos","year":"2004","journal-title":"Vaccine"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3992","DOI":"10.4049\/jimmunol.168.8.3992","article-title":"CD8+T cells required for primary immunity in C57BL\/6 mice following low dose, intradermal challenge with Leishmanai major","volume":"168","author":"Belkaid","year":"2002","journal-title":"J. Immunol."},{"key":"B4","first-page":"73","article-title":"Epidemiology of leishmaniasis in Tunisia","volume-title":"Tropical Communicable Diseases","author":"Ben Ismail","year":"1989"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1086\/498042","article-title":"The predictive validity of naturally acquired delayed-type hypersensitivity to leishmanin in resistance to Leishmania major\u2013associated cutaneous leishmaniasis","volume":"192","author":"Ben Salah","year":"2005","journal-title":"J. Inf. Dis."},{"key":"B6","doi-asserted-by":"crossref","first-page":"79","DOI":"10.5772\/65788","article-title":"Epidemiology of cutaneous leishmaniasis in Tunisia","volume-title":"The Epidemiology and Ecology of Leishmaniasis","author":"Bettaieb","year":"2017"},{"key":"B7","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1186\/1756-3305-7-386","article-title":"Prevalence and determinants of Leishmania major infection in emerging and old foci in Tunisia","volume":"7","author":"Bettaieb","year":"2014","journal-title":"Parasit. Vectors"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3232","DOI":"10.1128\/IAI.69.5.3232-3239.2001","article-title":"Flow cytometric determination of cellular sources and frequencies of key cytokine-producing lymphocytes directed against recombinant LACK and soluble Leishmania antigen in human cutaneous leishmaniasis","volume":"69","author":"Bottrel","year":"2001","journal-title":"Infect. Immun."},{"key":"B9","doi-asserted-by":"publisher","first-page":"126571263","DOI":"10.1086\/382031","article-title":"Analysis of granzyme B activity as a surrogate marker of Leishmania-specific cell mediated cytotoxicity in zoonotic cutaneous leismaniasis","volume":"189","author":"Bousoffara","year":"2004","journal-title":"J. Infect. Dis"},{"key":"B10","doi-asserted-by":"publisher","first-page":"4467","DOI":"10.1111\/j.1365-3083.2007.01964.x","article-title":"Parasite-driven in vitro human lymphocyte cytotoxicity against autologous infected macrophages from mucosal leishmaniasis","volume":"159","author":"Brodskyn","year":"1997","journal-title":"J. Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1128\/IAI.02404-14","article-title":"Protective and pathological functions of CD8+ T Cells in Leishmania braziliensis infection","volume":"83","author":"Cardoso","year":"2015","journal-title":"Infect. Immun."},{"key":"B12","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1111\/j.1365-2249.1990.tb05182.x","article-title":"Quantitative study of Leishmania braziliensis reactive T cells in peripheral blood and in the lesions of patients with American mucocutaneous leishmaniasis","volume":"79","author":"Concei\u00e7\u00e3o-Silva","year":"1990","journal-title":"Clin. Exp. Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2813","DOI":"10.1002\/eji.1830241135","article-title":"Leishmania major infection in mice primes for specific major histocompatibitlity complex class I\u2013restricted cytotoxic T cell responses","volume":"24","author":"da Concei\u00e7\u00e3o-Silva","year":"1994","journal-title":"Eur. J. Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1111\/j.1365-2133.2005.06647.x","article-title":"Flow cytometric analysis of cellular infiltrate from American tegumentary leishmaniasis lesions","volume":"153","author":"Da-Cruz","year":"2005","journal-title":"Br. J. Dermatol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1128\/CDLI.9.2.251-256.2002","article-title":"T-cell-mediated immune responses in patients with cutaneous or mucosal leishmaniasis: long-term evaluation after therapy","volume":"9","author":"Da-Cruz","year":"2002","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"B16","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1128\/IAI.62.6.2614-2618.1994","article-title":"Leishmania reactive CD4+ and CD8+ T cells associated with cure of human cutaneous leishmaniasis","volume":"62","author":"Da-Cruz","year":"1994","journal-title":"Infect. Immun."},{"key":"B17","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1590\/0037-8682-0174-2013","article-title":"CD8+ T cells in situ in different clinical forms of human cutaneous leishmaniasis","volume":"46","author":"Dantas","year":"2013","journal-title":"Rev. Soc. Bras. Med. Trop"},{"key":"B18","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1017\/S0950268800057964","article-title":"Cutaneous leishmaniasis in the Peruvian Andes: an epidemiological study of infection and immunity","volume":"114","author":"Davies","year":"1995","journal-title":"Epidemiol. Infect"},{"key":"B19","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S0001-706X(01)00181-4","article-title":"A randomized double-blind placebo-controlled trial to evaluate the immunogenicity of a candidate vaccine against American tegumentary leishmaniasis","volume":"80","author":"de Luca","year":"2001","journal-title":"Acta. Trop"},{"key":"B20","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1111\/cei.12798","article-title":"Effector memory CD4+ T cells differentially express activation associated molecules depending on the duration of American cutaneous leishmaniasis lesions","volume":"185","author":"de Oliveira Mendes-Aguiar","year":"2016","journal-title":"Clin. Exp. Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.vaccine.2011.11.005","article-title":"The development and clinical evaluation of second-generation leishmaniasis vaccines","volume":"30","author":"Duthie","year":"2012","journal-title":"Vaccine"},{"key":"B22","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1111\/j.1365-3024.2009.01125.x","article-title":"Recruitment of CD8+ T cells expressing granzyme A is associated with lesion progression in human cutaneous leishmaniasis","volume":"31","author":"Faria","year":"2009","journal-title":"Parasit. Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s12879-015-0799-x","article-title":"Apoptosis and frequency of total and effector CD8+ T lymphocytes from cutaneous leishmaniasis patients during antimonial therapy","volume":"19","author":"Ferraz","year":"2015","journal-title":"BMC Infect. Dis"},{"key":"B24","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1186\/s13071-017-2152-2","article-title":"CD3+CD4negCD8neg (double negative) T lymphocytes and NKT cells as the main cytotoxic-related-CD107a+cells in lesions of cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis","volume":"10","author":"Ferraz","year":"2017","journal-title":"Parasit. Vectors"},{"key":"B25","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1006\/clim.1999.4705","article-title":"Characterization of the local and systemic immune responses in patients with cutaneous leishmaniasis due to Leishmania major","volume":"91","author":"Gaafar","year":"1999","journal-title":"Clin. Immunol."},{"key":"B26","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/00034983.1971.11686746","article-title":"Natural and experimental re-infection of man with oriental score","volume":"65","author":"Guirges","year":"1971","journal-title":"Ann Trop Med Parasitol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"4906","DOI":"10.1128\/IAI.69.8.4906-4915.2001","article-title":"Heterogeneity of wild Leishmania major isolates in experimental murine pathogenicity and specific immune response","volume":"69","author":"K\u00e9ba\u00efer","year":"2001","journal-title":"Infect. Immun"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1016\/S0140-6736(00)03128-7","article-title":"Autoclaved Leishmania major vaccine for prevention of visceral leishmaniasis: a randomised, double-blind, BCG-controlled trial in Sudan","volume":"356","author":"Khalil","year":"2000","journal-title":"Lancet"},{"key":"B29","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0065-308X(08)60208-0","article-title":"Immunology of leishmaniasis","volume":"32","author":"Liew","year":"1993","journal-title":"Adv. Parasitol"},{"key":"B30","doi-asserted-by":"crossref","first-page":"5559","DOI":"10.1128\/IAI.67.11.5559-5566.1999","article-title":"Control of Leishmania infantum infection is associated with CD8+ and gamma interferon- and interleukin-5-producing CD4+ antigen-specific T cells","volume":"67","author":"Marry","year":"1999","journal-title":"Infect. Immun"},{"key":"B31","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1111\/j.1365-4632.2012.05850.x","article-title":"Reevaluating leishmanin skin test as a marker for immunity against cutaneous leishmaniasis","volume":"52","author":"Momeni Boroujeni","year":"2013","journal-title":"Int. J. Dermatol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"636039","DOI":"10.1155\/2014\/636039","article-title":"Involvement of different CD4+ T cell subsets producing granzyme B in the immune response to Leishmania major antigens","volume":"2014","author":"Naouar","year":"2014","journal-title":"Mediators. Inflamm."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e845","DOI":"10.1371\/journal.pntd.0000845","article-title":"CD8+ T cells as a source of IFN-gamma production in human cutaneous leishmaniasis","volume":"4","author":"Nateghi Rostami","year":"2010","journal-title":"PLoS. Negl. Trop. Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e1003504","DOI":"10.1371\/journal.ppat.1003504","article-title":"Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis","volume":"9","author":"Novais","year":"2013","journal-title":"PLoS Pathog."},{"key":"B35","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/s00281-015-0475-7","article-title":"CD8+ T cells in cutaneous leishmaniasis: the good, the bad, and the ugly","volume":"37","author":"Novais","year":"2015","journal-title":"Semin Immunopathol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/S1473-3099(07)70209-8","article-title":"Cutaneous leishmaniasis","volume":"7","author":"Reithinger","year":"2007","journal-title":"Lancet Infect. Dis"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1084\/jem.20020147","article-title":"Vaccination with heat-killed Leishmania antigen or recombinant leishmanial protein and CpG oligodeoxynucleotides induces long-term memory CD4+ and CD8+ T cell responses and protection against Leishmania major infection","volume":"195","author":"Rhee","year":"2002","journal-title":"J. Exp. Med"},{"key":"B38","first-page":"51","article-title":"Measure of effect and measures of associations","volume-title":"Modern Epidemiology","author":"Rothman","year":"2008"},{"key":"B39","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1111\/j.1365-3024.2007.00991.x","article-title":"CD8 cytotoxic T cells in cutaneous leishmaniasis","volume":"29","author":"Ruiz","year":"2007","journal-title":"Parasit. Immunol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1006\/expr.1999.4452","article-title":"Leishmania: na\u00efve human T cells sensitized with promastigote antigen and IL-12 develop into potent Th1 and CD8+ cytotoxic effectors","volume":"93","author":"Russo","year":"1999","journal-title":"Exp Parasitol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1038\/jid.2013.4","article-title":"CD8+ granzyme B+-mediated tissue injury vs. CD4+IFN gamma+-mediated parasite killing in human cutaneous leishmaniasis","volume":"133","author":"Santos","year":"2013","journal-title":"J. Invest. Dermatol."},{"key":"B42","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1046\/j.1365-2249.1999.00844.x","article-title":"Leishmanin skin test lymphoproliferative response and cytokine production after symptomatic or asymptomatic Leishmania major infection in Tunisia","volume":"116","author":"Sassi","year":"1999","journal-title":"Clin. Exp. Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1016\/S0140-6736(98)09552-X","article-title":"Randomised vaccine trial of single dose of killed Leishmania major plus BCG against anthroponotic cutaneous leishmaniasis in Bam, Iran","volume":"35","author":"Sharifi","year":"1998","journal-title":"Lancet"},{"key":"B44","first-page":"3610","article-title":"Extracellular granzymes A and B in humans: direction of native species during CTL responses in vitro and in vivo. J","volume":"160","author":"Spaeny-Dekking","year":"1998","journal-title":"Immunol"},{"key":"B45","first-page":"5","article-title":"CD8+ T cells in Leishmania infections: friends or foes?","volume":"24","author":"St\u00e4ger","year":"2012","journal-title":"Front. Immunol"},{"key":"B46","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/0471602396.ch6","article-title":"Counting Data","volume-title":"Biostatistics: A Methodology for the Health Sciences","author":"van Belle","year":"2004"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fcimb.2018.00397\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,15]],"date-time":"2020-11-15T04:46:34Z","timestamp":1605415594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fcimb.2018.00397\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,13]]},"references-count":46,"alternative-id":["10.3389\/fcimb.2018.00397"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2018.00397","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,13]]},"article-number":"397"}}