Fig. 4: ‘Resisters’ have decreased T cell responses to common mycobacterial antigens. | Nature Medicine

Fig. 4: ‘Resisters’ have decreased T cell responses to common mycobacterial antigens.

From: IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure

Fig. 4

a, COMPASS analysis identified five functionally relevant CD4 T cell subset responses to Peptide Pool 2 (Ag85A, Ag85B and TB10.4), which are summarized in the heatmap. Rows represent study subjects and columns CD4 T cell functional subsets. The depth of shading within the heatmap represents the probability of detecting a response above background. IFN-γ-containing subsets are noted in red. b, Subject-specific COMPASS results in response to stimulation with Peptide Pool 2 were summarized using the polyfunctionality score, which weights T cell subsets that include more than one function. The total number of subjects analyzed was 41. Boxplots show median and interquartile ranges. The statistical significance was calculated using the Mann–Whitney U test, and the two-tailed P value is indicated. c, Representative flow cytometry plots from a ‘resister’ and an LTBI subject show frequencies of IFN-γ+CD40L/CD154+IL-2+TNF+ T cells (red dots) in response to stimulation with Peptide Pool 2 or DMSO, with each experiment performed once. d, The absolute magnitude of Ag85/TB10.4-specific polyfunctional CD40L/CD154+ IL-2+ TNF+ CD4 T cells after background correction is displayed stratified by the expression of IFN-γ. These functional subsets represent the two right columns of the COMPASS plot in a. To facilitate visualization, we have not displayed a single LTBI outlier with the value of 3.41%. The total number of subjects analyzed was 41. Lines identify medians. The statistical significance was calculated using the Mann–Whitney U test, and two-tailed P values are indicated. e, COMPASS analysis identified 19 functionally relevant CD4 T cell subset responses to Mtb lysate, which are summarized in the heatmap. IFN-γ-containing subsets are noted in red. f, Polyfunctionality scores for the 41 subjects in response to Mtb lysate stimulation are shown, with boxplots representing median and interquartile ranges. The statistical significance was calculated using the Mann–Whitney U test, and the two-tailed P value is shown. g, Representative flow cytometry plots from a ‘resister’ and TST/IGRA-positive subject showing frequencies of IFN-γ+CD40L+IL-2+TNF+ T cells (red dots) in response to stimulation with Mtb lysate or DMSO are shown with each experiment performed once. h, The absolute magnitude of Mtb lysate-specific polyfunctional CD154+IL-2+TNF+ CD4 T cells after background correction is displayed, stratified by the expression of IFN-γ for 40 subjects, with lines representing medians. These functional subsets represent the 9th and 17th columns of the COMPASS plot in e. To facilitate visualization, we have not displayed a single LTBI outlier with a value of 12.61%. The statistical significance was calculated using the Mann–Whitney U test, and unadjusted two-tailed P values are shown.

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