Patients with Tuberculosis Disease Have Mycobacterium tuberculosis-Specific CD8 T Cells with a Pro-Apoptotic Phenotype and Impaired Proliferative Capacity, Which Is Not Restored following Treatment

• Type of Material: Article
• Authors: Cheryl Liane Day, Emory University; Noella D. Moshi, University of Cape Town; Deborah A. Abrahams, University of Cape Town; Michele van Rooyen, University of Cape Town; Terrence O'rie, University of Cape Town; Marwou de Kock, University of Cape Town; Willem A. Hanekom, University of Cape Town
• Language: English
• Date: 2014
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Day et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0094949
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 9
• Issue: 4
• Start Page: e94949
• End Page: e94949
• Grant/Funding Information: This work was supported in part by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (grant number R01 AI083156 to C.L.D.); Emory Center for AIDS Research (grant number P30 AI050409); a Collaborative Grant from the KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH) to N.D.M.; and a Mandela Rhodes Foundation fellowship to N.D.M.
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

Abstract

CD8 T cells play a critical role in control of chronic viral infections; however, the role of these cells in containing persistent bacterial infections, such as those caused by Mycobacterium tuberculosis (Mtb), is less clear. We assessed the phenotype and functional capacity of CD8 T cells specific for the immunodominant Mtb antigens CFP-10 and ESAT-6, in patients with pulmonary tuberculosis (TB) disease, before and after treatment, and in healthy persons with latent Mtb infection (LTBI). In patients with TB disease, CFP-10/ESAT-6-specific IFN-γ+ CD8 T cells had an activated, pro-apoptotic phenotype, with lower Bcl-2 and CD127 expression, and higher Ki67, CD57, and CD95 expression, than in LTBI. When CFP-10/ESAT-6-specific IFN-γ+ CD8 T cells were detectable, expression of distinct combinations of these markers was highly sensitive and specific for differentiating TB disease from LTBI. Successful treatment of disease resulted in changes of these markers, but not in restoration of CFP-10/ESAT-6-specific CD8 or CD4 memory T cell proliferative capacity. These data suggest that high mycobacterial load in active TB disease is associated with activated, short-lived CFP-10/ESAT-6-specific CD8 T cells with impaired functional capacity that is not restored following treatment. By contrast, LTBI is associated with preservation of long-lived CFP-10/ESAT-6-specific memory CD8 T cells that maintain high Bcl-2 expression and which may readily proliferate.