{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:13:27Z","timestamp":1790252007692,"version":"4.1.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2012,1,10]],"date-time":"2012-01-10T00:00:00Z","timestamp":1326153600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2012,1,10]],"date-time":"2012-01-10T00:00:00Z","timestamp":1326153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/srep00216","type":"journal-article","created":{"date-parts":[[2012,1,10]],"date-time":"2012-01-10T01:13:20Z","timestamp":1326158000000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Multifunctional CD4 T Cell Responses in Patients with Active Tuberculosis"],"prefix":"10.1038","volume":"2","author":[{"given":"Zhengang","family":"Qiu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiqun","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puxuan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Graner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boping","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinchun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,1,10]]},"reference":[{"key":"BFsrep00216_CR1","unstructured":"Organization, W. H. Global Tuberculosis Control. World Health Organization, Geneva, Switzerland. (2010)."},{"key":"BFsrep00216_CR2","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1146\/annurev.immunol.021908.132703","volume":"27","author":"AM Cooper","year":"2009","unstructured":"Cooper, A. M. Cell-mediated immune responses in tuberculosis. Annu Rev Immunol 27, 393\u2013422 (2009).","journal-title":"Annu Rev Immunol"},{"key":"BFsrep00216_CR3","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1038\/7701","volume":"21","author":"E Jouanguy","year":"1999","unstructured":"Jouanguy, E. et al. A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection. Nat Genet 21, 370\u20138 (1999).","journal-title":"Nat Genet"},{"key":"BFsrep00216_CR4","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/nm1592","volume":"13","author":"PA Darrah","year":"2007","unstructured":"Darrah, P. A. et al. Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med 13, 843\u201350 (2007).","journal-title":"Nat Med"},{"key":"BFsrep00216_CR5","doi-asserted-by":"publisher","first-page":"2665","DOI":"10.1002\/eji.200838336","volume":"38","author":"D Ciuffreda","year":"2008","unstructured":"Ciuffreda, D. et al. Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication. Eur J Immunol 38, 2665\u201377 (2008).","journal-title":"Eur J Immunol"},{"key":"BFsrep00216_CR6","doi-asserted-by":"publisher","first-page":"12071","DOI":"10.1128\/JVI.01261-07","volume":"81","author":"S Kannanganat","year":"2007","unstructured":"Kannanganat, S. et al. Human immunodeficiency virus type 1 controllers but not noncontrollers maintain CD4 T cells coexpressing three cytokines. J Virol 81, 12071\u20136 (2007).","journal-title":"J Virol"},{"key":"BFsrep00216_CR7","doi-asserted-by":"publisher","first-page":"4955","DOI":"10.4049\/jimmunol.181.7.4955","volume":"181","author":"EK Forbes","year":"2008","unstructured":"Forbes, E. K. et al. Multifunctional, high-level cytokine-producing Th1 cells in the lung, but not spleen, correlate with protection against Mycobacterium tuberculosis aerosol challenge in mice. J Immunol 181, 4955\u201364 (2008).","journal-title":"J Immunol"},{"key":"BFsrep00216_CR8","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1164\/rccm.200907-1011OC","volume":"180","author":"B Kalsdorf","year":"2009","unstructured":"Kalsdorf, B. et al. HIV-1 infection impairs the bronchoalveolar T-cell response to mycobacteria. Am J Respir Crit Care Med 180, 1262\u201370 (2009).","journal-title":"Am J Respir Crit Care Med"},{"key":"BFsrep00216_CR9","doi-asserted-by":"publisher","first-page":"2222","DOI":"10.4049\/jimmunol.1101122","volume":"187","author":"CL Day","year":"2011","unstructured":"Day, C. L. et al. Functional Capacity of Mycobacterium tuberculosis-Specific T Cell Responses in Humans Is Associated with Mycobacterial Load. J Immunol 187, 2222\u201332 (2011).","journal-title":"J Immunol"},{"key":"BFsrep00216_CR10","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.1002\/eji.201040455","volume":"40","author":"N Caccamo","year":"2010","unstructured":"Caccamo, N. et al. Multifunctional CD4(+) T cells correlate with active Mycobacterium tuberculosis infection. Eur J Immunol 40, 2211\u201320 (2010).","journal-title":"Eur J Immunol"},{"key":"BFsrep00216_CR11","doi-asserted-by":"publisher","first-page":"3527","DOI":"10.4049\/jimmunol.1003773","volume":"186","author":"JT Mattila","year":"2011","unstructured":"Mattila, J. T., Diedrich, C. R., Lin, P. L., Phuah, J. & Flynn, J. L. Simian immunodeficiency virus-induced changes in T cell cytokine responses in cynomolgus macaques with latent Mycobacterium tuberculosis infection are associated with timing of reactivation. J Immunol 186, 3527\u201337 (2011).","journal-title":"J Immunol"},{"key":"BFsrep00216_CR12","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1002\/eji.200838693","volume":"39","author":"JS Sutherland","year":"2009","unstructured":"Sutherland, J. S., Adetifa, I. M., Hill, P. C., Adegbola, R. A. & Ota, M. O. Pattern and diversity of cytokine production differentiates between Mycobacterium tuberculosis infection and disease. Eur J Immunol 39, 723\u20139 (2009).","journal-title":"Eur J Immunol"},{"key":"BFsrep00216_CR13","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.ejrad.2007.07.009","volume":"67","author":"JJ Lee","year":"2008","unstructured":"Lee, J. J., Chong, P. Y., Lin, C. B., Hsu, A. H. & Lee, C. C. High resolution chest CT in patients with pulmonary tuberculosis: characteristic findings before and after antituberculous therapy. Eur J Radiol 67, 100\u20134 (2008).","journal-title":"Eur J Radiol"},{"key":"BFsrep00216_CR14","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1097\/01.rti.0000213590.29472.ce","volume":"22","author":"F Ors","year":"2007","unstructured":"Ors, F. et al. High-resolution CT findings in patients with pulmonary tuberculosis: correlation with the degree of smear positivity. J Thorac Imaging 22, 154\u20139 (2007).","journal-title":"J Thorac Imaging"},{"key":"BFsrep00216_CR15","first-page":"560","volume":"14","author":"AC Hesseling","year":"2010","unstructured":"Hesseling, A. C. et al. Baseline sputum time to detection predicts month two culture conversion and relapse in non-HIV-infected patients. Int J Tuberc Lung Dis 14, 560\u201370 (2010).","journal-title":"Int J Tuberc Lung Dis"},{"key":"BFsrep00216_CR16","first-page":"807","volume":"123","author":"PG Gopi","year":"2006","unstructured":"Gopi, P. G. et al. Association of conversion & cure with initial smear grading among new smear positive pulmonary tuberculosis patients treated with Category I regimen. Indian J Med Res 123, 807\u201314 (2006).","journal-title":"Indian J Med Res"},{"key":"BFsrep00216_CR17","first-page":"91","volume":"6","author":"A El-Sony","year":"2002","unstructured":"El-Sony, A., Enarson, D., Khamis, A., Baraka, O. & Bjune, G. Relation of grading of sputum smears with clinical features of tuberculosis patients in routine practice in Sudan. Int J Tuberc Lung Dis 6, 91\u20137 (2002).","journal-title":"Int J Tuberc Lung Dis"},{"key":"BFsrep00216_CR18","doi-asserted-by":"publisher","first-page":"4187","DOI":"10.1128\/IAI.01392-09","volume":"78","author":"TM Wozniak","year":"2010","unstructured":"Wozniak, T. M., Saunders, B. M., Ryan, A. A. & Britton, W. J. Mycobacterium bovis BCG-specific Th17 cells confer partial protection against Mycobacterium tuberculosis infection in the absence of gamma interferon. Infect Immun 78, 4187\u201394 (2010).","journal-title":"Infect Immun"},{"key":"BFsrep00216_CR19","doi-asserted-by":"publisher","first-page":"4414","DOI":"10.4049\/jimmunol.0903332","volume":"184","author":"Y Okamoto Yoshida","year":"2010","unstructured":"Okamoto Yoshida, Y. et al. Essential role of IL-17A in the formation of a mycobacterial infection-induced granuloma in the lung. J Immunol 184, 4414\u201322 (2010).","journal-title":"J Immunol"},{"key":"BFsrep00216_CR20","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1111\/j.1365-3083.2011.02512.x","volume":"73","author":"D Qiao","year":"2011","unstructured":"Qiao, D. et al. ESAT-6- and CFP-10-specific Th1, Th22 and Th17 cells in tuberculous pleurisy may contribute to the local immune response against Mycobacterium tuberculosis infection. Scand J Immunol 73, 330\u20137 (2011).","journal-title":"Scand J Immunol"},{"key":"BFsrep00216_CR21","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1086\/648735","volume":"201","author":"S Babu","year":"2010","unstructured":"Babu, S., Bhat, S. Q., Kumar, N. P., Kumaraswami, V. & Nutman, T. B. Regulatory T cells modulate Th17 responses in patients with positive tuberculin skin test results. J Infect Dis 201, 20\u201331 (2010).","journal-title":"J Infect Dis"},{"key":"BFsrep00216_CR22","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1164\/rccm.200909-1463OC","volume":"181","author":"X Chen","year":"2010","unstructured":"Chen, X. et al. Reduced Th17 response in patients with tuberculosis correlates with IL-6R expression on CD4+ T Cells. Am J Respir Crit Care Med 181, 734\u201342 (2010).","journal-title":"Am J Respir Crit Care Med"},{"key":"BFsrep00216_CR23","doi-asserted-by":"publisher","first-page":"e11237","DOI":"10.1371\/journal.pone.0011237","volume":"5","author":"JM Young","year":"2010","unstructured":"Young, J. M., Adetifa, I. M., Ota, M. O. & Sutherland, J. S. Expanded polyfunctional T cell response to mycobacterial antigens in TB disease and contraction post-treatment. PLoS One 5, e11237 (2010).","journal-title":"PLoS One"},{"key":"BFsrep00216_CR24","doi-asserted-by":"publisher","first-page":"4725","DOI":"10.4049\/jimmunol.1003778","volume":"186","author":"S Metenou","year":"2011","unstructured":"Metenou, S. et al. Filarial infection suppresses malaria-specific multifunctional Th1 and Th17 responses in malaria and filarial coinfections. J Immunol 186, 4725\u201333 (2011).","journal-title":"J Immunol"},{"key":"BFsrep00216_CR25","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1136\/thx.2010.153825","volume":"66","author":"KC Jambo","year":"2011","unstructured":"Jambo, K. C. et al. Bronchoalveolar CD4+ T cell responses to respiratory antigens are impaired in HIV-infected adults. Thorax 66, 375\u201382 (2011).","journal-title":"Thorax"},{"key":"BFsrep00216_CR26","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1128\/iai.59.2.503-513.1991","volume":"59","author":"F Manca","year":"1991","unstructured":"Manca, F. et al. Limited clonal heterogeneity of antigen-specific T cells localizing in the pleural space during mycobacterial infection. Infect Immun 59, 503\u201313 (1991).","journal-title":"Infect Immun"},{"key":"BFsrep00216_CR27","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1086\/314852","volume":"180","author":"F Dieli","year":"1999","unstructured":"Dieli, F. et al. Sequestration of T lymphocytes to body fluids in tuberculosis: reversal of anergy following chemotherapy. J Infect Dis 180, 225\u20138 (1999).","journal-title":"J Infect Dis"},{"key":"BFsrep00216_CR28","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1084\/jem.191.8.1269","volume":"191","author":"MK Maini","year":"2000","unstructured":"Maini, M. K. et al. The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med 191, 1269\u201380 (2000).","journal-title":"J Exp Med"},{"key":"BFsrep00216_CR29","doi-asserted-by":"publisher","first-page":"e10469","DOI":"10.1371\/journal.pone.0010469","volume":"5","author":"IV Lyadova","year":"2011","unstructured":"Lyadova, I. V. et al. In mice, tuberculosis progression is associated with intensive inflammatory response and the accumulation of Gr-1 cells in the lungs. PLoS One 5, e10469 (2011).","journal-title":"PLoS One"},{"key":"BFsrep00216_CR30","doi-asserted-by":"publisher","first-page":"8456","DOI":"10.4049\/jimmunol.177.12.8456","volume":"177","author":"DO Co","year":"2006","unstructured":"Co, D. O. et al. Interactions between T cells responding to concurrent mycobacterial and influenza infections. J Immunol 177, 8456\u201365 (2006).","journal-title":"J Immunol"},{"key":"BFsrep00216_CR31","doi-asserted-by":"publisher","first-page":"3610","DOI":"10.1182\/blood-2009-05-223768","volume":"114","author":"E Volpe","year":"2009","unstructured":"Volpe, E. et al. Multiparametric analysis of cytokine-driven human Th17 differentiation reveals a differential regulation of IL-17 and IL-22 production. Blood 114, 3610\u20134 (2009).","journal-title":"Blood"},{"key":"BFsrep00216_CR32","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/cr.2009.138","volume":"20","author":"J Zhu","year":"2010","unstructured":"Zhu, J. & Paul, W. E. Heterogeneity and plasticity of T helper cells. Cell Res 20, 4\u201312 (2010).","journal-title":"Cell Res"},{"key":"BFsrep00216_CR33","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1182\/blood-2009-03-208249","volume":"114","author":"I Kryczek","year":"2009","unstructured":"Kryczek, I. et al. Phenotype, distribution, generation and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 114, 1141\u20139 (2009).","journal-title":"Blood"},{"key":"BFsrep00216_CR34","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1128\/CVI.00044-09","volume":"16","author":"X Chen","year":"2009","unstructured":"Chen, X. et al. Diagnosis of active tuberculosis in China using an in-house gamma interferon enzyme-linked immunospot assay. Clin Vaccine Immunol 16, 879\u201384 (2009).","journal-title":"Clin Vaccine Immunol"},{"key":"BFsrep00216_CR35","unstructured":"de Kantor, I. et al. Laboratory Services in Tuberculosis Control. World Health Organization, Geneva. (1998)."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep00216","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep00216.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep00216.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T04:51:18Z","timestamp":1672980678000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep00216"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,10]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2012,12,21]]}},"alternative-id":["BFsrep00216"],"URL":"https:\/\/doi.org\/10.1038\/srep00216","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,10]]},"assertion":[{"value":"12 October 2011","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 December 2011","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 January 2012","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"216"}}