Patients with tuberculosis disease have Mycobacterium tuberculosis-specific CD8 T cells with a pro-apoptotic phenotype and impaired proliferative capacity, which is not restored following treatment

dc.contributor.authorDay, Cheryl Len_ZA
dc.contributor.authorMoshi, Noella Den_ZA
dc.contributor.authorAbrahams, Deborah Aen_ZA
dc.contributor.authorVan Rooyen, Micheleen_ZA
dc.contributor.authorO'rie, Terrenceen_ZA
dc.contributor.authorDe Kock, Marwouen_ZA
dc.contributor.authorHanekom, Willem Aen_ZA
dc.date.accessioned2015-11-11T14:27:22Z
dc.date.available2015-11-11T14:27:22Z
dc.date.issued2014en_ZA
dc.description.abstractCD8 T cells play a critical role in control of chronic viral infections; however, the role of these cells in containing persistent bacterial infections, such as those caused by Mycobacterium tuberculosis (Mtb), is less clear. We assessed the phenotype and functional capacity of CD8 T cells specific for the immunodominant Mtb antigens CFP-10 and ESAT-6, in patients with pulmonary tuberculosis (TB) disease, before and after treatment, and in healthy persons with latent Mtb infection (LTBI). In patients with TB disease, CFP-10/ESAT-6-specific IFN-γ + CD8 T cells had an activated, pro-apoptotic phenotype, with lower Bcl-2 and CD127 expression, and higher Ki67, CD57, and CD95 expression, than in LTBI. When CFP-10/ESAT-6-specific IFN-γ + CD8 T cells were detectable, expression of distinct combinations of these markers was highly sensitive and specific for differentiating TB disease from LTBI. Successful treatment of disease resulted in changes of these markers, but not in restoration of CFP-10/ESAT-6-specific CD8 or CD4 memory T cell proliferative capacity. These data suggest that high mycobacterial load in active TB disease is associated with activated, short-lived CFP-10/ESAT-6-specific CD8 T cells with impaired functional capacity that is not restored following treatment. By contrast, LTBI is associated with preservation of long-lived CFP-10/ESAT-6-specific memory CD8 T cells that maintain high Bcl-2 expression and which may readily proliferate.en_ZA
dc.identifier.apacitationDay, C. L., Moshi, N. D., Abrahams, D. A., Van Rooyen, M., O'rie, T., De Kock, M., & Hanekom, W. A. (2014). Patients with tuberculosis disease have Mycobacterium tuberculosis-specific CD8 T cells with a pro-apoptotic phenotype and impaired proliferative capacity, which is not restored following treatment. <i>PLoS One</i>, http://hdl.handle.net/11427/14922en_ZA
dc.identifier.chicagocitationDay, Cheryl L, Noella D Moshi, Deborah A Abrahams, Michele Van Rooyen, Terrence O'rie, Marwou De Kock, and Willem A Hanekom "Patients with tuberculosis disease have Mycobacterium tuberculosis-specific CD8 T cells with a pro-apoptotic phenotype and impaired proliferative capacity, which is not restored following treatment." <i>PLoS One</i> (2014) http://hdl.handle.net/11427/14922en_ZA
dc.identifier.citationDay, C. L., Moshi, N. D., Abrahams, D. A., van Rooyen, M., O'rie, T., de Kock, M., & Hanekom, W. A. (2014). Patients with tuberculosis disease have Mycobacterium tuberculosis-specific CD8 T cells with a pro-apoptotic phenotype and impaired proliferative capacity, which is not restored following treatment. PloS one, 9(4). doi:10.1371/journal.pone.0094949en_ZA
dc.identifier.ris TY - Journal Article AU - Day, Cheryl L AU - Moshi, Noella D AU - Abrahams, Deborah A AU - Van Rooyen, Michele AU - O'rie, Terrence AU - De Kock, Marwou AU - Hanekom, Willem A AB - CD8 T cells play a critical role in control of chronic viral infections; however, the role of these cells in containing persistent bacterial infections, such as those caused by Mycobacterium tuberculosis (Mtb), is less clear. We assessed the phenotype and functional capacity of CD8 T cells specific for the immunodominant Mtb antigens CFP-10 and ESAT-6, in patients with pulmonary tuberculosis (TB) disease, before and after treatment, and in healthy persons with latent Mtb infection (LTBI). In patients with TB disease, CFP-10/ESAT-6-specific IFN-γ + CD8 T cells had an activated, pro-apoptotic phenotype, with lower Bcl-2 and CD127 expression, and higher Ki67, CD57, and CD95 expression, than in LTBI. When CFP-10/ESAT-6-specific IFN-γ + CD8 T cells were detectable, expression of distinct combinations of these markers was highly sensitive and specific for differentiating TB disease from LTBI. Successful treatment of disease resulted in changes of these markers, but not in restoration of CFP-10/ESAT-6-specific CD8 or CD4 memory T cell proliferative capacity. These data suggest that high mycobacterial load in active TB disease is associated with activated, short-lived CFP-10/ESAT-6-specific CD8 T cells with impaired functional capacity that is not restored following treatment. By contrast, LTBI is associated with preservation of long-lived CFP-10/ESAT-6-specific memory CD8 T cells that maintain high Bcl-2 expression and which may readily proliferate. DA - 2014 DB - OpenUCT DO - 10.1371/journal.pone.0094949 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Patients with tuberculosis disease have Mycobacterium tuberculosis-specific CD8 T cells with a pro-apoptotic phenotype and impaired proliferative capacity, which is not restored following treatment TI - Patients with tuberculosis disease have Mycobacterium tuberculosis-specific CD8 T cells with a pro-apoptotic phenotype and impaired proliferative capacity, which is not restored following treatment UR - http://hdl.handle.net/11427/14922 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14922
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0094949
dc.identifier.vancouvercitationDay CL, Moshi ND, Abrahams DA, Van Rooyen M, O'rie T, De Kock M, et al. Patients with tuberculosis disease have Mycobacterium tuberculosis-specific CD8 T cells with a pro-apoptotic phenotype and impaired proliferative capacity, which is not restored following treatment. PLoS One. 2014; http://hdl.handle.net/11427/14922.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentSouth African Tuberculosis Vaccine Initiative (SATVI)en_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2014 Day et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherCytotoxic T cellsen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherPhenotypesen_ZA
dc.titlePatients with tuberculosis disease have Mycobacterium tuberculosis-specific CD8 T cells with a pro-apoptotic phenotype and impaired proliferative capacity, which is not restored following treatmenten_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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