High Frequencies of Caspase-3 Expressing Mycobacterium tuberculosis-Specific CD4(+) T Cells Are Associated With Active Tuberculosis

• Type of Material: Conference Paper
• Authors: Toidi Adekambi, Emory University; Chris Ibegbu, Emory University; Stephanie Cagle, Emory University; Susan M Ray, Emory University; Jyothi Rengarajan, Emory University
• Language: English
• Date: 2018-06-25
• Publisher: Emory University Libraries
• Publication Version: Final Published Version
• Copyright Statement: © 2018 Adekambi, Ibegbu, Cagle, Ray and Rengarajan.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fimmu.2018.01481
• Title of Journal or Parent Work: Frontiers in Immunology
• Conference or Event Name: Annual Meeting of the American-Association-of-Immunologists (AAI)
• Volume: 9
• Issue: JUN
• Start Page: 1481
• End Page: 1481
• Grant/Funding Information: An Emory-CFAR R03 Developmental grant (to TA) from Core grant P30AI050409, a pilot project grant awarded (to JR) from the NIH CCHI Grant AI057266, an Emory Global Health Institute Faculty Distinction Award (to JR), and the Yerkes National Primate Center base grant RR000165, a Center For AIDS Research (CFAR) Immunology Core grant P30AI050409 (to Emory University).
• Keywords: latent Mtb infection; active tuberculosis; DIAGNOSIS; monitoring; LYMPHOCYTE STIMULATION; HIV-1 INFECTION; Life Sciences & Biomedicine; APOPTOSIS; Science & Technology; BIOMARKERS; CENTRAL MEMORY; caspase-3(+)IFN-gamma(+)CD4(+) T cells; anti-tuberculosis treatment; UP-REGULATION; LATENT TUBERCULOSIS; Immunology; DISEASE-ACTIVITY; tuberculosis; ACTIVATION
• Research Categories: Health Sciences, Immunology; Biology, Microbiology

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 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.