Monitoring CD27 Expression to Evaluate Mycobacterium Tuberculosis Activity in HIV-1 Infected Individuals In Vivo

University of Stellenbosch, South Africa
PLoS ONE (Impact Factor: 3.23). 11/2011; 6(11):e27284. DOI: 10.1371/journal.pone.0027284
Source: PubMed

ABSTRACT The level of bacterial activity is only poorly defined during asymptomatic Mycobacterium tuberculosis (MTB) infection. The objective was to study the capacity of a new biomarker, the expression of the T cell maturation marker CD27 on MTB-specific CD4 T cells, to identify active tuberculosis (TB) disease in subjects from a MTB and HIV endemic region. The frequency and CD27 expression of circulating MTB-specific CD4 T cells was determined in 96 study participants after stimulation with purified protein derivative (PPD) using intracellular cytokine staining for IFNgamma (IFNγ). Subjects were then stratified by their TB and HIV status. Within PPD responders, a CD27(-) phenotype was associated with active TB in HIV(-) (p = 0.0003) and HIV(+) (p = 0.057) subjects, respectively. In addition, loss of CD27 expression preceded development of active TB in one HIV seroconverter. Interestingly, in contrast to HIV(-) subjects, MTB-specific CD4 T cell populations from HIV(+) TB-asymptomatic subjects were often dominated by CD27(-) cells. These data indicate that down-regulation of CD27 on MTB-specific CD4 T cell could be used as a biomarker of active TB, potentially preceding clinical TB disease. Furthermore, these data are consistent with the hypothesis that late, chronic HIV infection is frequently associated with increased mycobacterial activity in vivo. The analysis of T cell maturation and activation markers might thus be a useful tool to monitor TB disease progression.

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Available from: Michael Hoelscher, Sep 28, 2015
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    • "The study by Sloot et al. supports the concept that a diagnostic approach based on host biomarkers cannot only improve the diagnosis of active TB in populations where a conventional sputum-based diagnosis is difficult (e.g. in children, HIV-positives, extra-pulmonary TB), but might further allow identification of subjects with sub-clinically active M.tb replication. Other recent articles also highlighted the potential of host biomarkers based on transcriptional (Anderson et al., 2014; Joosten et al., 2012) or novel Tcel lsignatures (Portevin et al., 2014; Harari et al., 2011; Schuetz et al., 2011) to improve diagnosis of active TB and possibly also allow early detection of TB disease progression. It is widely accepted that often a substantial time interval exists between infection with M.tb, and diagnosis of symptomatic disease. "
    02/2015; 370(2). DOI:10.1016/j.ebiom.2015.01.009
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    • "Very recently, Petruccioli et al. have correlated bifunctional “RD1-proteins”-specific-CD4 T cells with effector memory phenotype with active TB disease, while “RD1-proteins”-specific-CD4 T cells with a central memory phenotype were associated with cured TB and LTBI subjects (82). According to this study, the EM phenotype should be associated with inactive TB due to the presence of live and replicating bacteria, whereas the contraction of this phenotype and the further differentiation toward CM T cells in LTBI and cured TB subjects could indicate Mtb control, suggesting that the different expression of the memory/effector status may be used to monitor treatment efficacy, as previously suggested in patients with active TB with HIV co-infection (82, 97, 98). "
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    ABSTRACT: With 1.4 million deaths and 8.7 million new cases in 2011, tuberculosis (TB) remains a global health care problem and together with HIV and Malaria represents the one of the three infectious diseases world-wild. Control of the global TB epidemic has been impaired by the lack of an effective vaccine, by the emergence of drug-resistant forms of Mycobacterium tuberculosis (Mtb) and by the lack of sensitive and rapid diagnostics. It is estimated, by epidemiological reports, that one third of the world’s population is latently infected with Mtb, but the majority of infected individuals develops long-lived protective immunity, which controls and contains Mtb in a T cell-dependent manner. Development of TB disease results from interactions among the environment, the host, and the pathogen, and known risk factors include HIV coinfection, immunodeficiency, diabetes mellitus, overcrowding, malnutrition, and general poverty; therefore an effective T cell response determines whether the infection resolves or develops into clinically evident disease. Consequently, there is great interest in determining which T cells subsets mediate anti-mycobacterial immunity, delineating their effector functions. On the other hand, many aspects remain unsolved in understanding why some individuals are protected from Mtb infection while others go on to develop disease.Several studies have demonstrated that CD4+ T cells are involved in protection against Mtb, as supported by the evidence that CD4+ T cell depletion is responsible for Mtb reactivation in HIV-infected individuals. There are many subsets of CD4+ T cells, such as T-helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs), and all these subsets cooperate or interfere with each other to control infection; the dominant subset may differ between active and latent Mtb infection cases. Mtb-specific CD4+ Th1 cell response is considered to have a protective role for the ability to produce cytokines such as IFN- or TNF- that contribute to
    Frontiers in Immunology 04/2014; 5:180. DOI:10.3389/fimmu.2014.00180
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    ABSTRACT: During HIV infection, it is unclear why different opportunistic pathogens cause disease at different CD4 T cell count thresholds. Early work has shown that CD4 T cell depletion is influenced both by cellular activation status and expression of viral entry receptors. More recently, functional characteristics of the CD4 T cells, such as cytokine and chemokine production, have also been shown to influence cellular susceptibility to HIV. Here, we examine how functional differences in pathogen-specific CD4 T cells could lead to their differential loss during HIV infection. This may have implications for when different opportunistic infections occur, and a better understanding of the mechanisms for functional imprinting of antigen-specific T cells may lead to improvements in design of vaccines against HIV and opportunistic pathogens.
    Trends in Immunology 03/2012; 33(5):207-14. DOI:10.1016/ · 10.40 Impact Factor
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