TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection
Fig 1
Cytokine expression in antigen-specific CD4+ and CD8+ T cells is diminished following chronic M. tuberculosis infection.
(A) Representative flow cytometry data showing the frequency of ESAT6-tetramer+ CD4+ T cells after M. tuberculosis infection. At each time point, lung cells were stimulated in vitro with the ESAT61-15 peptide or anti-CD3/CD28 mAbs to measure IFNγ and TNF expression. (B) The frequency of TB10.4-tetramer+ CD8+ T cells after M. tuberculosis infection. At each of time point, lung cells were stimulated in vitro with the TB10.44−11 peptide or anti-CD3/CD28 mAbs and IFNγ and TNF production was measured. (C) Representative flow cytometry data of ESAT6-tetramer CD4+ T cells at d19 or d84 post infection. IL-2, IFNγ, and TNF production after stimulation with ESAT61-15 peptide. (D) The fraction of ESAT-specific CD4+ T cells that make IL-2, IFNγ, and TNF on d19 (unfilled), w12 (striped), or w17 (filled) post infection. (E) The fraction of the number of cytokines being produced by ESAT6-specefic CD4+ T cells. (F) The fraction of CD4+ T cells producing IL-2, IFNγ, and TNF on d19 (unfilled), w12 (striped), or w17 (filled) post infection. (G) The percentage of IFNγ-producing CD4+ and CD8+ T cells that also make TNF over the course of infection. (H) The fraction of ESAT6-specific CD4+ T cells and bacterial burden in the lungs as d19, w12, and w17 post infection. All data is representative of three independent experiments with at least five mice per time point. *p<0.05, **p<0.01, ***p<0.001, one-way anova compared. Bars represent mean ± SEM. The “background” cytokine production, defined as cytokine production that occurs in the absence of specific stimulation was subtracted for each sample before calculations or normalizations were performed.