{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:05:34Z","timestamp":1790849134475,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2009,4,23]],"date-time":"2009-04-23T00:00:00Z","timestamp":1240444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Program of Founding Research Centers for Emerging"},{"name":"Reemerging Infectious Diseases"},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for Promotion of Science","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Japanese Ministry of Education, Science and Culture"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,4,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In vivo administration of IL-15 at the contraction phase in BCG infection inhibited apoptosis of effector CD8+ T cells resulting in the significant increase of Ag-specific memory CD8+ T cells.<\/jats:p>\n               <jats:p>We reported previously that IL-15 plays a critical role in protecting effector CD8+ T cells from apoptosis during the contraction phase following acute infection with Listeria monocytogenes by inducing antiapoptotic molecules. In the present study, we examined the effects of in vivo administration of rIL-15 on contraction of CD8+ T cells after chronic infection with Mycobacterium bovis BCG and on the efficacy of BCG vaccination against Mycobacterium tuberculosis infection. Antigen-specific CD8+ T cells reached an expansion peak at approximately Day 21, followed by a contraction after inoculation with rBCG expressing OVA. In vivo administration of rIL-15 from Days 22 to 42 after BCG inoculation inhibited apoptosis of effector CD8+ T cells by up-regulating their Bcl-2 expression, resulting in a significant increase of antigen-specific memory CD8+ T cells producing IFN-\u03b3. However, the IL-15 treatment did not elicit improved efficacy of BCG vaccination against M. tuberculosis. These results suggest that IL-15 plays a critical role in protecting activated CD8+ T cells from apoptosis during the contraction phase following BCG inoculation, although IL-15 administration alone at the contraction phase might not be sufficient to protect the efficient memory T cell responses against subsequent infection with M. tuberculosis.<\/jats:p>","DOI":"10.1189\/jlb.0608363","type":"journal-article","created":{"date-parts":[[2009,4,24]],"date-time":"2009-04-24T00:34:52Z","timestamp":1240533292000},"page":"187-194","source":"Crossref","is-referenced-by-count":16,"title":["IL-15 protects antigen-specific CD8+ T cell contraction after <i>Mycobacterium bovis<\/i> bacillus Calmette-Gu\u00e9rin infection"],"prefix":"10.1093","volume":"86","author":[{"given":"Ce","family":"Tang","sequence":"first","affiliation":[{"name":"Division of Host Defense, Medical Institute of Bioregulation, Kyushu University , Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisakata","family":"Yamada","sequence":"additional","affiliation":[{"name":"Division of Host Defense, Medical Institute of Bioregulation, Kyushu University , Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Shibata","sequence":"additional","affiliation":[{"name":"Division of Host Defense, Medical Institute of Bioregulation, Kyushu University , Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Kyushu University , Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Worawidh","family":"Wajjwalku","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine, Kasetsart University , Nakhonpathom, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunobu","family":"Yoshikai","sequence":"additional","affiliation":[{"name":"Division of Host Defense, Medical Institute of Bioregulation, Kyushu University , Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,4,23]]},"reference":[{"key":"2023032919304594200_jlb0187-cit-b1","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1001\/jama.282.7.677","article-title":"Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project","volume":"282","author":"Dye","year":"1999","journal-title":"JAMA"},{"key":"2023032919304594200_jlb0187-cit-b2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1542\/peds.96.1.29","article-title":"The efficacy of bacillus Calmette-Guerin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature","volume":"96","author":"Colditz","year":"1995","journal-title":"Pediatrics"},{"key":"2023032919304594200_jlb0187-cit-b3","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.coi.2007.05.005","article-title":"Apoptosis and the homeostatic control of immune responses","volume":"19","author":"Hildeman","year":"2007","journal-title":"Curr. Opin. Immunol."},{"key":"2023032919304594200_jlb0187-cit-b4","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S1074-7613(00)80478-1","article-title":"The Fas\/Fas ligand pathway and Bcl-2 regulate T cell responses to model self and foreign antigens","volume":"8","author":"Van Parijs","year":"1998","journal-title":"Immunity"},{"key":"2023032919304594200_jlb0187-cit-b5","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1084\/jem.185.2.189","article-title":"The common cytokine receptor \u03b3 chain plays an essential role in regulating lymphoid homeostasis","volume":"185","author":"Nakajima","year":"1997","journal-title":"J. Exp. Med."},{"key":"2023032919304594200_jlb0187-cit-b6","doi-asserted-by":"crossref","first-page":"3810","DOI":"10.1073\/pnas.95.7.3810","article-title":"Cytokine-induced survival of activated T cells in vitro and in vivo","volume":"95","author":"Vella","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023032919304594200_jlb0187-cit-b7","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3109\/08830189809042995","article-title":"Interleukin-2, interleukin-15, and their receptors","volume":"16","author":"Waldmann","year":"1998","journal-title":"Int. Rev. Immunol."},{"key":"2023032919304594200_jlb0187-cit-b8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1084\/jem.191.1.157","article-title":"Differential roles of interleukin 15 mRNA isoforms generated by alternative splicing in immune responses in vivo","volume":"191","author":"Nishimura","year":"2000","journal-title":"J. Exp. Med."},{"key":"2023032919304594200_jlb0187-cit-b9","doi-asserted-by":"crossref","first-page":"946","DOI":"10.4049\/jimmunol.167.2.946","article-title":"Overexpression of IL-15 in vivo enhances protection against Mycobacterium bovis bacillus Calmette-Gu\u00e9rin infection via augmentation of NK and T cytotoxic 1 responses","volume":"167","author":"Umemura","year":"2001","journal-title":"J. Immunol."},{"key":"2023032919304594200_jlb0187-cit-b10","doi-asserted-by":"crossref","first-page":"6045","DOI":"10.1128\/IAI.71.10.6045-6048.2003","article-title":"Interleukin-15 as an immune adjuvant to increase the efficacy of Mycobacterium bovis bacillus Calmette-Gu\u00e9rin vaccination","volume":"71","author":"Umemura","year":"2003","journal-title":"Infect. Immun."},{"key":"2023032919304594200_jlb0187-cit-b11","doi-asserted-by":"crossref","first-page":"2496","DOI":"10.4049\/jimmunol.176.4.2496","article-title":"Impaired protection against Mycobacterium bovis bacillus Calmette-Guerin infection in IL-15-deficient mice","volume":"176","author":"Saito","year":"2006","journal-title":"J. Immunol."},{"key":"2023032919304594200_jlb0187-cit-b12","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1002\/eji.200535290","article-title":"Interleukin-15 mediates protection against experimental tuberculosis: a role for NKG2D-dependent effector mechanisms of CD8+ T cells","volume":"36","author":"Rausch","year":"2006","journal-title":"Eur. J. Immunol."},{"key":"2023032919304594200_jlb0187-cit-b13","doi-asserted-by":"crossref","first-page":"2910","DOI":"10.1128\/IAI.73.5.2910-2922.2005","article-title":"Induction of Mycobacterium tuberculosis-specific primary and secondary T-cell responses in interleukin-15-deficient mice","volume":"73","author":"Lazarevic","year":"2005","journal-title":"Infect. Immun."},{"key":"2023032919304594200_jlb0187-cit-b14","doi-asserted-by":"crossref","first-page":"507","DOI":"10.4049\/jimmunol.176.1.507","article-title":"IL-15 regulates CD8+ T cell contraction during primary infection","volume":"176","author":"Yajima","year":"2006","journal-title":"J. Immunol."},{"key":"2023032919304594200_jlb0187-cit-b15","article-title":"Guide for the Care and Use of Laboratory Animals","author":"Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council","year":"1996","edition":"7th ed."},{"key":"2023032919304594200_jlb0187-cit-b16","doi-asserted-by":"crossref","first-page":"5737","DOI":"10.4049\/jimmunol.168.11.5737","article-title":"Multiple mechanisms compensate to enhance tumor-protective CD8+ T cell response in the long-term despite poor CD8+ T cell priming initially: comparison between an acute versus a chronic intracellular bacterium expressing a model antigen","volume":"168","author":"Dudani","year":"2002","journal-title":"J. Immunol."},{"key":"2023032919304594200_jlb0187-cit-b17","doi-asserted-by":"crossref","first-page":"5341","DOI":"10.4049\/jimmunol.174.9.5341","article-title":"Reducing the stimulation of CD8+ T cells during infection with intracellular bacteria promotes differentiation primarily into a central (CD62LhighCD44high) subset","volume":"174","author":"Van Faassen","year":"2005","journal-title":"J. Immunol."},{"key":"2023032919304594200_jlb0187-cit-b18","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1126\/science.1058867","article-title":"Preferential localization of effector memory cells in nonlymphoid tissue","volume":"291","author":"Masopust","year":"2001","journal-title":"Science"},{"key":"2023032919304594200_jlb0187-cit-b19","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1128\/IAI.68.5.2962-2970.2000","article-title":"Interleukin-7 or interleukin-15 enhances survival of Mycobacterium tuberculosis-infected mice","volume":"68","author":"Maeurer","year":"2000","journal-title":"Infect. Immun."},{"key":"2023032919304594200_jlb0187-cit-b20","doi-asserted-by":"crossref","first-page":"211","DOI":"10.4049\/jimmunol.179.1.211","article-title":"A reduced antigen load in vivo, rather than weak inflammation, causes a substantial delay in CD8+ T cell priming against Mycobacterium bovis (bacillus Calmette-Gu\u00e9rin)","volume":"179","author":"Russell","year":"2007","journal-title":"J. Immunol."},{"key":"2023032919304594200_jlb0187-cit-b21","doi-asserted-by":"crossref","first-page":"9419","DOI":"10.1128\/JVI.79.15.9419-9429.2005","article-title":"Role of thymic output in regulating CD8 T-cell homeostasis during acute and chronic viral infection","volume":"79","author":"Miller","year":"2005","journal-title":"J. Virol."},{"key":"2023032919304594200_jlb0187-cit-b22","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.immuni.2007.12.017","article-title":"Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity","volume":"28","author":"Hughes","year":"2008","journal-title":"Immunity"},{"key":"2023032919304594200_jlb0187-cit-b23","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1146\/annurev.immunol.19.1.93","article-title":"Immunology of tuberculosis","volume":"19","author":"Flynn","year":"2001","journal-title":"Annu. Rev. Immunol."},{"key":"2023032919304594200_jlb0187-cit-b24","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1073\/pnas.95.1.270","article-title":"Human cytolytic and interferon \u03b3-secreting CD8+ T lymphocytes specific for Mycobacterium tuberculosis","volume":"95","author":"Lalvani","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023032919304594200_jlb0187-cit-b25","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1084\/jem.193.10.1213","article-title":"Induction of M3-restricted cytotoxic T lymphocyte responses by N-formylated peptides derived from Mycobacterium tuberculosis","volume":"193","author":"Chun","year":"2001","journal-title":"J. Exp. Med."},{"key":"2023032919304594200_jlb0187-cit-b26","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1128\/iai.52.1.293-302.1986","article-title":"Properties of proteins MPB64, MPB70, and MPB80 of Mycobacterium bovis BCG","volume":"52","author":"Harboe","year":"1986","journal-title":"Infect. Immun."},{"key":"2023032919304594200_jlb0187-cit-b27","doi-asserted-by":"crossref","first-page":"3806","DOI":"10.4049\/jimmunol.178.6.3806","article-title":"H2\u2013M3-restricted CD8+ T cells induced by peptide-pulsed dendritic cells confer protection against Mycobacterium tuberculosis","volume":"178","author":"Doi","year":"2007","journal-title":"J. Immunol."},{"key":"2023032919304594200_jlb0187-cit-b28","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1086\/586902","article-title":"Efficacy of recombinant bacille Calmette-Gu\u00e9rin vaccine secreting interleukin-15\/antigen 85B fusion protein in providing protection against Mycobacterium tuberculosis","volume":"197","author":"Tang","year":"2008","journal-title":"J. Infect. Dis."},{"key":"2023032919304594200_jlb0187-cit-b29","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1084\/jem.20020369","article-title":"Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells","volume":"195","author":"Becker","year":"2002","journal-title":"J.Exp. Med."},{"key":"2023032919304594200_jlb0187-cit-b30","doi-asserted-by":"crossref","first-page":"4827","DOI":"10.4049\/jimmunol.168.10.4827","article-title":"Cutting edge: requirement for IL-15 in the generation of primary and memory antigen-specific CD8 T cells","volume":"168","author":"Schluns","year":"2002","journal-title":"J. Immunol."},{"key":"2023032919304594200_jlb0187-cit-b31","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1084\/jem.20020772","article-title":"Interleukin 15 controls both proliferation and survival of a subset of memoryphenotype CD8+ T cells","volume":"196","author":"Judge","year":"2002","journal-title":"J. Exp. Med."}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1189%2Fjlb.0608363","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/api.wiley.com\/onlinelibrary\/chorus\/v1\/articles\/10.1189%2Fjlb.0608363","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/86\/1\/187\/49606782\/jlb0187.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/86\/1\/187\/49606782\/jlb0187.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T15:57:17Z","timestamp":1680191837000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/86\/1\/187\/6959561"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4,23]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2009,4,23]]},"published-print":{"date-parts":[[2009,4,23]]}},"URL":"https:\/\/doi.org\/10.1189\/jlb.0608363","relation":{},"ISSN":["1938-3673","0741-5400"],"issn-type":[{"value":"1938-3673","type":"electronic"},{"value":"0741-5400","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,7]]},"published":{"date-parts":[[2009,4,23]]}}}