{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T01:30:39Z","timestamp":1768440639522,"version":"3.49.0"},"reference-count":27,"publisher":"American Society for Microbiology","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>We describe here the application of a novel bovine interleukin-2 (IL-2) enzyme-linked immunosorbent assay (ELISA) for the measurement of antigen-specific IL-2 in cattle naturally infected with<jats:named-content content-type=\"genus-species\">Mycobacterium bovis<\/jats:named-content>and in cattle vaccinated with<jats:named-content content-type=\"genus-species\">Mycobacterium bovis<\/jats:named-content>BCG and then experimentally challenged with pathogenic<jats:named-content content-type=\"genus-species\">M. bovis<\/jats:named-content>. Supernatants from whole-blood cultures stimulated with mycobacterial antigen (bovine purified protein derivative [PPDB] or the peptide cocktail ESAT6-CFP10) were assessed using a sandwich ELISA consisting of a new recombinant monoclonal fragment capture antibody and a commercially available polyclonal anti-bovine-IL-2. The production of IL-2 was compared to the production of gamma interferon (IFN-\u03b3) in the same antigen-stimulated whole-blood supernatants. The data show that cattle infected with<jats:named-content content-type=\"genus-species\">M. bovis<\/jats:named-content>produced quantifiable levels of antigen-specific IL-2, while IL-2 levels in cattle vaccinated with<jats:named-content content-type=\"genus-species\">M. bovis<\/jats:named-content>BCG did not. Furthermore, cattle vaccinated with<jats:named-content content-type=\"genus-species\">M. bovis<\/jats:named-content>BCG and then challenged with pathogenic<jats:named-content content-type=\"genus-species\">M. bovis<\/jats:named-content>displayed a more rapid induction of IL-2 but ultimately had lower levels of infection-induced IL-2 than did unvaccinated challenge control cattle. These data suggest that IL-2 responses are not detectable post-BCG vaccination and that these responses may require infection with virulent<jats:named-content content-type=\"genus-species\">M. bovis<\/jats:named-content>to develop. This may be useful to differentiate infected cattle from uninfected or BCG-vaccinated cattle, although the overall sensitivity is relatively low, particularly in single intradermal comparative cervical tuberculin (SICCT)-negative infected animals. Furthermore, the strength of the IL-2 response may correlate with pathology, which poses interesting questions on the immunobiology of bovine tuberculosis in contrast to human tuberculosis, which is discussed.<\/jats:p>","DOI":"10.1128\/cvi.00522-13","type":"journal-article","created":{"date-parts":[[2013,10,31]],"date-time":"2013-10-31T00:43:57Z","timestamp":1383180237000},"page":"39-45","source":"Crossref","is-referenced-by-count":18,"title":["Use of Antigen-Specific Interleukin-2 To Differentiate between Cattle Vaccinated with Mycobacterium bovis BCG and Cattle Infected with M. bovis"],"prefix":"10.1128","volume":"21","author":[{"given":"Shelley G.","family":"Rhodes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy C.","family":"McKinna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Steinbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilly S.","family":"Dean","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernardo","family":"Villarreal-Ramos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam O.","family":"Whelan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Pirson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gareth J.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek","family":"Clifford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. Martin","family":"Vordermeier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","published-online":{"date-parts":[[2013,10,30]]},"reference":[{"key":"key20180919073718_B1","doi-asserted-by":"publisher","first-page":"6996","DOI":"10.1128\/IAI.70.12.6996-7003.2002","article-title":"Identification of novel Mycobacterium tuberculosis antigens with potential as diagnostic reagents or subunit vaccine candidates by comparative genomics","volume":"70","author":"Cockle","year":"2002","journal-title":"Infect. Immun."},{"key":"key20180919073718_B2","doi-asserted-by":"publisher","first-page":"1946","DOI":"10.1128\/CVI.00377-10","article-title":"Simultaneous measurement of antigen stimulated interleukin-1\u03b2 and gamma interferon production enhances test sensitivity for the detection of Mycobacterium bovis infection in cattle","volume":"17","author":"Jones","year":"2010","journal-title":"Clin. Vaccine Immunol."},{"key":"key20180919073718_B3","doi-asserted-by":"publisher","first-page":"e21566","DOI":"10.1371\/journal.pone.0021566","article-title":"Systemic BCG immunization induces persistent lung mucosal multifunctional CD4 T(EM) cells which expand following virulent mycobacterial challenge","volume":"6","author":"Kaveh","year":"2011","journal-title":"PLoS One"},{"key":"key20180919073718_B4","doi-asserted-by":"publisher","first-page":"2902","DOI":"10.1016\/j.vaccine.2011.02.010","article-title":"Vaccine-induced anti-tuberculosis protective immunity in mice correlates with the magnitude and quality of multifunctional CD4 T cells","volume":"29","author":"Derrick","year":"2011","journal-title":"Vaccine"},{"key":"key20180919073718_B5","doi-asserted-by":"publisher","first-page":"8047","DOI":"10.4049\/jimmunol.0801592","article-title":"Tuberculosis subunit vaccination provides long-term protective immunity characterized by multifunctional CD4 memory T cells","volume":"182","author":"Lindenstrom","year":"2009","journal-title":"J. Immunol."},{"key":"key20180919073718_B6","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.tube.2011.11.004","article-title":"Distinct polyfunctional CD4+ T cell responses to BCG, ESAT-6 and CFP-10 in tuberculous pleurisy","volume":"92","author":"Li","year":"2012","journal-title":"Tuberculosis (Edinb.)"},{"key":"key20180919073718_B7","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.1002\/eji.201040455","article-title":"Multifunctional CD4(+) T cells correlate with active Mycobacterium tuberculosis infection","volume":"40","author":"Caccamo","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"key20180919073718_B8","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.cyto.2008.05.002","article-title":"Mycobacterium tuberculosis-specific CD4+ IFNgamma+ and TNFalpha+ multifunctional memory T cells co-express GM-CSF","volume":"43","author":"Mueller","year":"2008","journal-title":"Cytokine"},{"key":"key20180919073718_B9","doi-asserted-by":"crossref","first-page":"5217","DOI":"10.4049\/jimmunol.178.8.5217","article-title":"Dynamic relationship between IFN-gamma and IL-2 profile of Mycobacterium tuberculosis-specific T cells and antigen load","volume":"178","author":"Millington","year":"2007","journal-title":"J. Immunol."},{"key":"key20180919073718_B10","doi-asserted-by":"publisher","first-page":"e39909","DOI":"10.1371\/journal.pone.0039909","article-title":"The HyVac4 subunit vaccine efficiently boosts BCG-primed anti-mycobacterial protective immunity","volume":"7","author":"Billeskov","year":"2012","journal-title":"PLoS One"},{"key":"key20180919073718_B11","doi-asserted-by":"publisher","first-page":"6311","DOI":"10.4049\/jimmunol.1300248","article-title":"Control of chronic Mycobacterium tuberculosis infection by CD4 KLRG1-IL-2-secreting central memory cells","volume":"190","author":"Lindenstrom","year":"2013","journal-title":"J. Immunol."},{"key":"key20180919073718_B12","doi-asserted-by":"publisher","first-page":"e29194","DOI":"10.1371\/journal.pone.0029194","article-title":"Development of an antibody to bovine IL-2 reveals multifunctional CD4 T(EM) cells in cattle naturally infected with bovine tuberculosis","volume":"6","author":"Whelan","year":"2011","journal-title":"PLoS One"},{"key":"key20180919073718_B13","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1046\/j.1365-2567.2000.00944.x","article-title":"Bovine tuberculosis: immune responses in the peripheral blood and at the site of active infection","volume":"99","author":"Rhodes","year":"2000","journal-title":"Immunology"},{"key":"key20180919073718_B14","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.1128\/IAI.68.5.2573-2578.2000","article-title":"Antigen specificity in experimental bovine tuberculosis","volume":"68","author":"Rhodes","year":"2000","journal-title":"Infect. Immun."},{"key":"key20180919073718_B15","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.vetmic.2010.08.019","article-title":"Vaccines designed to protect against Mycobacterium tuberculosis infection may aid the identification of novel vaccine constructs and diagnostic antigens for bovine tuberculosis","volume":"148","author":"Pirson","year":"2011","journal-title":"Vet. Microbiol."},{"key":"key20180919073718_B16","doi-asserted-by":"publisher","first-page":"5453","DOI":"10.1016\/j.vaccine.2011.05.057","article-title":"Lack of correlation between BCG-induced tuberculin skin test sensitisation and protective immunity in cattle","volume-title":"Vaccine","author":"Whelan","year":"2011"},{"key":"key20180919073718_B17","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1128\/CDLI.11.4.729-735.2004","article-title":"Use of recombinant ESAT-6:CFP-10 fusion protein for differentiation of infections of cattle by Mycobacterium bovis and by M. avium subsp. avium and M. avium subsp. paratuberculosis","volume-title":"Clin. Diagn. Lab. Immunol.","author":"Waters","year":"2004"},{"key":"key20180919073718_B18","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1128\/CVI.00442-09","article-title":"Immune responses in cattle inoculated with Mycobacterium bovis, M. tuberculosis or M. kansasii","volume":"17","author":"Waters","year":"2010","journal-title":"Clin. Vaccine Immunol."},{"key":"key20180919073718_B19","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1086\/428950","article-title":"ESAT-6 and CFP-10 in clinical versus environmental isolates of Mycobacterium kansasii","volume":"191","author":"Arend","year":"2005","journal-title":"J. Infect. Dis."},{"key":"key20180919073718_B20","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1128\/CVI.00116-07","article-title":"Assessment of the cross-reacticity between Mycobacterium bovis and M. kansasii ESAT-6 and CFP-10 at the T-cell epitope level","volume":"14","author":"Vordermeier","year":"2007","journal-title":"Clin. Vaccine Immunol."},{"key":"key20180919073718_B21","doi-asserted-by":"publisher","first-page":"3026","DOI":"10.1128\/IAI.70.6.3026-3032.2002","article-title":"Correlation of ESAT6-specific gamma-interferon production with pathology in cattle following Mycobacterium bovis-BCG vaccination against experimental bovine tuberculosis","volume":"70","author":"Vordermeier","year":"2002","journal-title":"Infect. Immun."},{"key":"key20180919073718_B22","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1051\/vetres\/2009062","article-title":"Repeat tuberculin skin testing leads to desensitization in naturally infected tuberculous cattle which is associated with elevated interleukin-10 and decreased interleukin-1-beta responses","volume":"41","author":"Coad","year":"2010","journal-title":"Vet. Res."},{"key":"key20180919073718_B23","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1111\/j.1469-0691.2009.03104.x","article-title":"Detection of interleukin-2 in addition to interferon-gamma discriminates active tuberculosis patients, latently infected individuals, and controls","volume":"16","author":"Biselli","year":"2010","journal-title":"Clin. Microbiol. Infect."},{"key":"key20180919073718_B24","doi-asserted-by":"publisher","first-page":"e46041","DOI":"10.1371\/journal.pone.0046041","article-title":"Potential role of M. tuberculosis specific IFN-\u03b3 and IL-2 ELISPOT assays in discriminating children with active or latent tuberculosis","volume":"7","author":"Chiappini","year":"2012","journal-title":"PLoS One"},{"key":"key20180919073718_B25","doi-asserted-by":"publisher","first-page":"e17813","DOI":"10.1371\/journal.pone.0017813","article-title":"Whole-blood flow-cytometric analysis of antigen-specific CD4 T-cell cytokine profiles distinguishes active tuberculosis from non-active states","volume":"6","author":"Sester","year":"2011","journal-title":"PLoS One"},{"key":"key20180919073718_B26","doi-asserted-by":"publisher","first-page":"e15619","DOI":"10.1371\/journal.pone.0015619","article-title":"Enumeration of functional T-cell subsets by fluorescence-immunospot defines signatures of pathogen burden in tuberculosis","volume":"5","author":"Casey","year":"2010","journal-title":"PLoS One"},{"key":"key20180919073718_B27","doi-asserted-by":"publisher","first-page":"e1001237","DOI":"10.1371\/journal.ppat.1001237","article-title":"Hypoxia induces an immunodominant target of tuberculosis specific T cells absent from common BCG vaccines","volume":"6","author":"Gideon","year":"2010","journal-title":"PLoS Pathog."}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1128\/CVI.00522-13","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T20:50:02Z","timestamp":1627591802000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00522-13"}},"subtitle":[],"editor":[{"given":"W. R.","family":"Waters","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2013,10,30]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2013,12,31]]},"published-print":{"date-parts":[[2014,1]]}},"alternative-id":["10.1128\/CVI.00522-13"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00522-13","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,30]]}}}