Activation Profile of Mycobacterium tuberculosis-Specific CD4(+) T Cells Reflects Disease Activity Irrespective of HIV Status - PubMed (original) (raw)

Activation Profile of Mycobacterium tuberculosis-Specific CD4(+) T Cells Reflects Disease Activity Irrespective of HIV Status

Katalin A Wilkinson et al. Am J Respir Crit Care Med. 2016.

No abstract available

PubMed Disclaimer

Figures

Figure 1.

Figure 1.

Comparison of the activation profile of IFN-γ+ early secretory antigenic target-6/culture filtrate protein-10–specific CD4+ T cells between HIV-uninfected and HIV-infected individuals with latent tuberculosis infection (LTBI) or active tuberculosis (aTB). (A) Representative overlay plots of human leukocyte antigen-DR (HLA-DR), CD38, and Ki-67 expression in total CD4+ T cells (gray) and IFN-γ+ Mycobacterium tuberculosis (Mtb)-specific CD4+ T cells (red). (B) Expression of HLA-DR, Ki67, and CD38 on IFN-γ+ Mtb-specific CD4+ T cells in LTBI/HIV− (n = 16), aTB/HIV− (n = 15), LTBI /HIV+ (n = 16), and aTB/HIV+ (n = 18) participants. Open circles depict LTBI individuals, solid circles represent smear-positive patients with aTB, and crosses correspond to smear-negative and culture-positive individuals with aTB. Horizontal lines indicate the median. Statistical comparisons were performed using a nonparametric Mann-Whitney U test. (C) Receiver operating characteristic curves and specificity/sensitivity crossover plots for HLA-DR expression level in IFN-γ+ Mtb-specific CD4+ T cells to discriminate between LTBI or aTB in HIV-uninfected and HIV-infected individuals. The area under the curve (AUC), P value, and confidence intervals (CIs) are shown. The diagonal dashed line depicts an AUC of 0.5, representing a random test. The dashed vertical line on the crossover plots represents the optimal threshold to distinguish LTBI and aTB individuals.

Figure 2.

Figure 2.

Comparison of the polyfunctional profile of early secretory antigenic target-6 (ESAT-6)/culture filtrate protein-10 (CFP-10)–specific CD4+ T cells between HIV-uninfected and HIV-infected individuals with latent tuberculosis infection (LTBI) or active tuberculosis (aTB). (A) Representative dot plots of IFN-γ, tumor necrosis factor (TNF)-α, and IL-2 production in response to ESAT-6/CFP-10 peptide pool in one LTBI/HIV− individual. NS = no stimulation. Numbers represent the frequencies of cytokine-producing cells expressed as a percentage of the total CD4+ T-cell population. (B) Proportion of Mycobacterium tuberculosis (Mtb)-specific CD4+ T cells producing any possible combinations of IFN-γ, TNF-α, or IL-2. Horizontal bars represent the median values and interquartile range. Statistical analysis was performed using Mann-Whitney test; significant differences are indicated by asterisks (***P < 0.001, **P < 0.01, *P < 0.05). Each slice of the pie corresponds to a distinct combination of cytokine. A key to colors used in the pie charts is shown at the bottom of the graph. (C) Receiver operating characteristic curves and specificity/sensitivity crossover plots for the proportion of IFN-γ+ IL-2+ TNF-α+ (top), and IFN-γ+ IL-2−TNF-α+ (bottom) Mtb-specific CD4+ T cells to discriminate between LTBI or aTB in HIV-uninfected and HIV-infected individuals. The diagonal dashed line depicts an area under the curve (AUC) of 0.5, representing a random test. The dashed vertical line on the crossover plots represents the optimal threshold to distinguish LTBI and aTB individuals. CI = confidence interval.

References

    1. Gardiner JL, Karp CL. Transformative tools for tackling tuberculosis. J Exp Med. 2015;212:1759–1769. -PMC -PubMed
    1. Harari A, Rozot V, Bellutti Enders F, Perreau M, Stalder JM, Nicod LP, Cavassini M, Calandra T, Blanchet CL, Jaton K, et al. Dominant TNF-α+ Mycobacterium tuberculosis-specific CD4+ T cell responses discriminate between latent infection and active disease. Nat Med. 2011;17:372–376. -PMC -PubMed
    1. Lichtner M, Mascia C, Sauzullo I, Mengoni F, Vita S, Marocco R, Belvisi V, Russo G, Vullo V, Mastroianni CM. Multifunctional analysis of CD4+ T-cell response as immune-based model for tuberculosis detection. J Immunol Res. 2015;2015:217287. -PMC -PubMed
    1. Portevin D, Moukambi F, Clowes P, Bauer A, Chachage M, Ntinginya NE, Mfinanga E, Said K, Haraka F, Rachow A, et al. Assessment of the novel T-cell activation marker-tuberculosis assay for diagnosis of active tuberculosis in children: a prospective proof-of-concept study. Lancet Infect Dis. 2014;14:931–938. -PubMed
    1. Adekambi T, Ibegbu CC, Cagle S, Kalokhe AS, Wang YF, Hu Y, Day CL, Ray SM, Rengarajan J. Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response. J Clin Invest. 2015;125:3723. -PMC -PubMed

Publication types

MeSH terms

Grants and funding

LinkOut - more resources