AUTHOR=Adekambi Toidi , Ibegbu Chris C. , Cagle Stephanie , Ray Susan M. , Rengarajan Jyothi TITLE=High Frequencies of Caspase-3 Expressing Mycobacterium tuberculosis-Specific CD4+ T Cells Are Associated With Active Tuberculosis JOURNAL=Frontiers in Immunology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01481 DOI=10.3389/fimmu.2018.01481 ISSN=1664-3224 ABSTRACT=

Antigen-specific CD4⁺ T cell responses to Mycobacterium tuberculosis (Mtb) infection are important for host defense against tuberculosis (TB). However, Mtb-specific IFN-γ-producing T cells do not distinguish active tuberculosis (ATB) patients from individuals with asymptomatic latent Mtb infection (LTBI). We reasoned that the immune phenotype of Mtb-specific IFN-γ⁺CD4⁺ T cells could provide an indirect gauge of Mtb antigen load within individuals. We sought to identify immune markers in Mtb-specific IFN-γ⁺CD4⁺ T cells and hypothesized that expression of caspase-3 Mtb-specific CD4⁺ T cells would be associated with ATB. Using polychromatic flow cytometry, we evaluated the expression of caspase-3 in Mtb-specific CD4⁺ T cells from LTBI and ATB as well as from ATB patients undergoing anti-TB treatment. We found significantly higher frequencies of Mtb-specific caspase-3⁺IFN-γ⁺CD4⁺ T cells in ATB compared to LTBI. Caspase-3⁺IFN-γ⁺CD4⁺ T cells were also more activated compared to their caspase-3-negative counterparts. Furthermore, the frequencies of caspase-3⁺IFN-γ⁺CD4⁺ T cells decreased in response to anti-TB treatment. Our studies suggest that the frequencies of caspase-3-expressing antigen-specific CD4⁺ T cells may reflect mycobacterial burden in vivo and may be useful for distinguishing Mtb infection status along with other host biomarkers.