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PD-1 expression on mycobacterium tuberculosis-specific CD4 T cells is associated with bacterial load in human tuberculosis

dc.contributor.authorDay, Cheryl L.en_ZA
dc.contributor.authorAbrahams, Deborah A.en_ZA
dc.contributor.authorBunjun, Rubinaen_ZA
dc.contributor.authorStone, Lynnetten_ZA
dc.contributor.authorDe Kock, Marwouen_ZA
dc.contributor.authorWalzl, Gerharden_ZA
dc.contributor.authorWilkinson, Robert J.en_ZA
dc.contributor.authorBurgers, Wendy A.en_ZA
dc.contributor.authorHanekom, Willem A.en_ZA
dc.date.accessioned2019-09-25T12:39:57Z
dc.date.available2019-09-25T12:39:57Z
dc.date.issued2018
dc.identifier.citationDay, C. L., et al. 2018. PD-1 expression on mycobacterium tuberculosis-specific CD4 T cells is associated with bacterial load in human tuberculosis. Frontiers in Immunology, 9:1995, doi:10.3389/fimmu.2018.01995
dc.identifier.issn1664-3224 (online)
dc.identifier.otherdoi:10.3389/fimmu.2018.01995
dc.identifier.urihttp://hdl.handle.net/10019.1/106521
dc.descriptionCITATION: Day, C. L., et al. 2018. PD-1 expression on mycobacterium tuberculosis-specific CD4 T cells is associated with bacterial load in human tuberculosis. Frontiers in Immunology, 9:1995, doi:10.3389/fimmu.2018.01995.
dc.descriptionThe original publication is available at https://www.frontiersin.org
dc.description.abstractENGLISH ABSTRACT: Persistent antigen stimulation in chronic infections has been associated with antigen-specific T cell dysfunction and upregulation of inhibitory receptors, including programmed cell death protein 1 (PD-1). Pulmonary tuberculosis (TB) disease is characterized by high levels of Mycobacterium tuberculosis (Mtb), yet the relationship between bacterial load, PD-1 expression, and Mtb-specific T cell function in human TB has not been well-defined. Using peripheral blood samples from adults with LTBI and with pulmonary TB disease, we tested the hypothesis that PD-1 expression is associated with bacterial load and functional capacity of Mtb-specific T cell responses. We found that PD-1 was expressed at significantly higher levels on Th1 cytokine-producing Mtb-specific CD4 T cells from patients with smear-positive TB, compared with smear-negative TB and LTBI, which decreased after completion of anti-TB treatment. By contrast, expression of PD-1 on Mtb-specific CD8 T cells was significantly lower than on Mtb-specific CD4 T cells and did not differ by Mtb infection and disease status. In vitro stimulation of PBMC with Mtb antigens demonstrated that PD-1 is induced on proliferating Mtb-specific CD4 T cells and that Th1 cytokine production capacity is preferentially maintained within PD-1+ proliferating CD4 T cells, compared with proliferating Mtb-specific CD4 T cells that lack PD-1 expression. Together, these data indicate that expression of PD-1 on Mtb-specific CD4 T cells is indicative of mycobacterial antigen exposure and identifies a population of effector cells with Th1 cytokine production capacity. These studies provide novel insights into the role of the PD-1 pathway in regulating CD4 and CD8 T cell responses in Mtb infection and provide rationale for future studies to evaluate PD-1 expression on antigen-specific CD4 T cells as a potential biomarker for bacterial load and treatment response in human TB.en_ZA
dc.description.urihttps://www.frontiersin.org/articles/10.3389/fimmu.2018.01995/full
dc.format.extent18 pagesen_ZA
dc.language.isoen_ZAen_ZA
dc.publisherFrontiers Mediaen_ZA
dc.subjectTuberculosisen_ZA
dc.subjectMycobacterium tuberculosisen_ZA
dc.subjectViruses -- Receptorsen_ZA
dc.subjectViral cell transformationen_ZA
dc.titlePD-1 expression on mycobacterium tuberculosis-specific CD4 T cells is associated with bacterial load in human tuberculosisen_ZA
dc.typeArticleen_ZA
dc.description.versionPublisher's version
dc.rights.holderAuthors retain copyrighten_ZA


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