A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion

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dc.contributor.authorRiou, Catherineen_ZA
dc.contributor.authorGray, Clive Men_ZA
dc.contributor.authorLugongolo, Masixoleen_ZA
dc.contributor.authorGwala, Thabisileen_ZA
dc.contributor.authorKiravu, Aganoen_ZA
dc.contributor.authorDeniso, Pamelaen_ZA
dc.contributor.authorStewart-Isherwood, Lynseyen_ZA
dc.contributor.authorOmar, Shaheed Vallyen_ZA
dc.contributor.authorGrobusch, Martin Pen_ZA
dc.contributor.authorCoetzee, Gerriten_ZA
dc.date.accessioned2015-11-23T12:35:26Z
dc.date.available2015-11-23T12:35:26Z
dc.date.issued2014en_ZA
dc.description.abstractWe investigated 18 HIV-negative patients with MDR-TB for M. tuberculosis (Mtb)- and PPD-specific CD4 T cell responses and followed them over 6 months of drug therapy. Twelve of these patients were sputum culture (SC) positive and six patients were SC negative upon enrollment. Our aim was to identify a subset of mycobacteria-specific CD4 T cells that would predict time to culture conversion. The total frequency of mycobacteria-specific CD4 T cells at baseline could not distinguish patients showing positive or negative SC. However, a greater proportion of late-differentiated (LD) Mtb- and PPD-specific memory CD4 T cells was found in SC positive patients than in those who were SC negative (p = 0.004 and p = 0.0012, respectively). Similarly, a higher co-expression of HLA-DR + Ki67 + on Mtb- and PPD-specific CD4 T cells could also discriminate between sputum SC positive versus SC negative (p = 0.004 and p = 0.001, respectively). Receiver operating characteristic (ROC) analysis revealed that baseline levels of Ki67 + HLA-DR + Mtb- and PPD-specific CD4 T cells were predictive of the time to sputum culture conversion, with area-under-the-curve of 0.8 (p = 0.027). Upon treatment, there was a significant decline of these Ki67 + HLA-DR + T cell populations in the first 2 months, with a progressive increase in mycobacteria-specific polyfunctional IFNγ + IL2 + TNFα + CD4 T cells over 6 months. Thus, a subset of activated and proliferating mycobacterial-specific CD4 T cells (Ki67 + HLA-DR + ) may provide a valuable marker in peripheral blood that predicts time to sputum culture conversion in TB patients at the start of treatment.en_ZA
dc.identifier.apacitationRiou, C., Gray, C. M., Lugongolo, M., Gwala, T., Kiravu, A., Deniso, P., ... Coetzee, G. (2014). A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion. <i>PLoS One</i>, http://hdl.handle.net/11427/15330en_ZA
dc.identifier.chicagocitationRiou, Catherine, Clive M Gray, Masixole Lugongolo, Thabisile Gwala, Agano Kiravu, Pamela Deniso, Lynsey Stewart-Isherwood, Shaheed Vally Omar, Martin P Grobusch, and Gerrit Coetzee "A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion." <i>PLoS One</i> (2014) http://hdl.handle.net/11427/15330en_ZA
dc.identifier.citationRiou, C., Gray, C. M., Lugongolo, M., Gwala, T., Kiravu, A., Deniso, P., ... & Fallows, D. (2014). A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion. PloS one, 9(7), e102178. doi:10.1371/journal.pone.0102178en_ZA
dc.identifier.ris TY - Journal Article AU - Riou, Catherine AU - Gray, Clive M AU - Lugongolo, Masixole AU - Gwala, Thabisile AU - Kiravu, Agano AU - Deniso, Pamela AU - Stewart-Isherwood, Lynsey AU - Omar, Shaheed Vally AU - Grobusch, Martin P AU - Coetzee, Gerrit AB - We investigated 18 HIV-negative patients with MDR-TB for M. tuberculosis (Mtb)- and PPD-specific CD4 T cell responses and followed them over 6 months of drug therapy. Twelve of these patients were sputum culture (SC) positive and six patients were SC negative upon enrollment. Our aim was to identify a subset of mycobacteria-specific CD4 T cells that would predict time to culture conversion. The total frequency of mycobacteria-specific CD4 T cells at baseline could not distinguish patients showing positive or negative SC. However, a greater proportion of late-differentiated (LD) Mtb- and PPD-specific memory CD4 T cells was found in SC positive patients than in those who were SC negative (p = 0.004 and p = 0.0012, respectively). Similarly, a higher co-expression of HLA-DR + Ki67 + on Mtb- and PPD-specific CD4 T cells could also discriminate between sputum SC positive versus SC negative (p = 0.004 and p = 0.001, respectively). Receiver operating characteristic (ROC) analysis revealed that baseline levels of Ki67 + HLA-DR + Mtb- and PPD-specific CD4 T cells were predictive of the time to sputum culture conversion, with area-under-the-curve of 0.8 (p = 0.027). Upon treatment, there was a significant decline of these Ki67 + HLA-DR + T cell populations in the first 2 months, with a progressive increase in mycobacteria-specific polyfunctional IFNγ + IL2 + TNFα + CD4 T cells over 6 months. Thus, a subset of activated and proliferating mycobacterial-specific CD4 T cells (Ki67 + HLA-DR + ) may provide a valuable marker in peripheral blood that predicts time to sputum culture conversion in TB patients at the start of treatment. DA - 2014 DB - OpenUCT DO - 10.1371/journal.pone.0102178 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion TI - A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion UR - http://hdl.handle.net/11427/15330 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15330
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0102178
dc.identifier.vancouvercitationRiou C, Gray CM, Lugongolo M, Gwala T, Kiravu A, Deniso P, et al. A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion. PLoS One. 2014; http://hdl.handle.net/11427/15330.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Immunologyen_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 Riou 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.otherT helper cellsen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherSputumen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherMulti-drug-resistant tuberculosisen_ZA
dc.subject.otherMitogensen_ZA
dc.subject.otherDrug therapyen_ZA
dc.subject.otherMemory T cellsen_ZA
dc.titleA subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversionen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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