Frequency of Mycobacterium tuberculosis-specific CD8+ T-cells in the course of anti-tuberculosis treatment

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dc.contributor.authorAxelsson-Robertson, Rebeccaen_ZA
dc.contributor.authorRao, Martinen_ZA
dc.contributor.authorLoxton, Andre G.en_ZA
dc.contributor.authorWalzl, Gerharden_ZA
dc.contributor.authorBates, Matthewen_ZA
dc.contributor.authorZumla, Alimuddinen_ZA
dc.contributor.authorMaeurer, Markusen_ZA
dc.date.accessioned2018-08-27T09:41:19Z
dc.date.available2018-08-27T09:41:19Z
dc.date.issued2015
dc.descriptionCITATION: Axelsson-Robertson, R. et al. 2015. Frequency of Mycobacterium tuberculosis-specific CD8+ T-cells in the course of anti-tuberculosis treatment. International Journal of Infectious Diseases, 32:23–29, doi:10.1016/j.ijid.2015.01.017.
dc.descriptionThe original publication is available at https://www.journals.elsevier.com/international-journal-of-infectious-diseases
dc.description.abstractAnti-tuberculosis drug treatment is known to affect the number, phenotype, and effector functionality of antigen-specific T-cells. In order to objectively gauge Mycobacterium tuberculosis (MTB)-specific CD8+ T-cells at the single-cell level, we developed soluble major histocompatibility complex (MHC) class I multimers/peptide multimers, which allow analysis of antigen-specific T-cells without ex vivo manipulation or functional tests. We constructed 38 MHC class I multimers covering some of the most frequent MHC class I alleles (HLA-A*02:01, A*24:02, A*30:01, A*30:02, A*68:01, B*58:01, and C*07:01) pertinent to a South African or Zambian population, and presenting the following MTB-derived peptides: the early expressed secreted antigens TB10.4 (Rv0288), Ag85B (Rv1886c), and ESAT-6 (Rv3875), as well as intracellular enzymes, i.e., glycosyltransferase 1 (Rv2957), glycosyltransferase 2 (Rv2958c), and cyclopropane fatty acid synthase (Rv0447c). Anti-TB treatment appeared to impact on the frequency of multimer-positive CD8+ T-cells, with a general decrease after 6 months of therapy. Also, a reduction in the total central memory CD8+ T-cell frequencies, as well as the antigen-specific compartment in CD45RA−CCR7+ T-cells was observed. We discuss our findings on the basis of differential dynamics of MTB-specific T-cell frequencies, impact of MTB antigen load on T-cell phenotype, and antigen-specific T-cell responses in tuberculosis.en_ZA
dc.description.versionPublisher's version
dc.format.extent7 pages
dc.identifier.citationAxelsson-Robertson, R. et al. 2015. Frequency of Mycobacterium tuberculosis-specific CD8+ T-cells in the course of anti-tuberculosis treatment. International Journal of Infectious Diseases, 32:23–29, doi:10.1016/j.ijid.2015.01.017.
dc.identifier.issn1201-9712 (online)
dc.identifier.otherdoi:10.1016/j.ijid.2015.01.017
dc.identifier.urihttp://hdl.handle.net/10019.1/104350
dc.language.isoen_ZAen_ZA
dc.publisherElsevier
dc.rights.holderAuthors retain copyright
dc.subjectTuberculosisen_ZA
dc.subjectTuberculosis -- Treatmenten_ZA
dc.titleFrequency of Mycobacterium tuberculosis-specific CD8+ T-cells in the course of anti-tuberculosis treatmenten_ZA
dc.typeArticleen_ZA
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