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.author Riou, Catherine en_ZA
dc.contributor.author Gray, Clive M en_ZA
dc.contributor.author Lugongolo, Masixole en_ZA
dc.contributor.author Gwala, Thabisile en_ZA
dc.contributor.author Kiravu, Agano en_ZA
dc.contributor.author Deniso, Pamela en_ZA
dc.contributor.author Stewart-Isherwood, Lynsey en_ZA
dc.contributor.author Omar, Shaheed Vally en_ZA
dc.contributor.author Grobusch, Martin P en_ZA
dc.contributor.author Coetzee, Gerrit en_ZA
dc.date.accessioned 2015-11-23T12:35:26Z
dc.date.available 2015-11-23T12:35:26Z
dc.date.issued 2014 en_ZA
dc.identifier.citation Riou, 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.0102178 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/15330
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0102178
dc.description.abstract 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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This 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.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other T helper cells en_ZA
dc.subject.other Mycobacterium tuberculosis en_ZA
dc.subject.other Sputum en_ZA
dc.subject.other Tuberculosis en_ZA
dc.subject.other Multi-drug-resistant tuberculosis en_ZA
dc.subject.other Mitogens en_ZA
dc.subject.other Drug therapy en_ZA
dc.subject.other Memory T cells en_ZA
dc.title A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2014 Riou et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Immunology en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Riou, 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/11427/15330 en_ZA
dc.identifier.chicagocitation Riou, 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/11427/15330 en_ZA
dc.identifier.vancouvercitation Riou 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.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


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This 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. Except where otherwise noted, this item's license is described as This 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.