Persistent expression of activation markers on Mycobacterium tuberculosis-specific CD4 T cells in smear negative TB patients

• Authors: Ahmed Esmael, Debre Markos University; Adane Mihret, Addis Ababa University; Tamrat Abebe, Addis Ababa University; Daniel Mussa, Armauer Hansen Research Institute; Sebsibe Neway, Armauer Hansen Research Institute; Joel Ernst, University of California, San Francisco; Jyothi Rengarajan, Emory University; Liya Wassie, Armauer Hansen Research Institute; Rawleigh Howe, Emory University
• Journal Title: PLoS ONE
• Volume: Volume 17, Number 8 August
• Publisher: PLoS ONE | 2022-08-01, Pages e0271234-e0271234
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1371/journal.pone.0271234
• Subjects: Biology, Microbiology; Health Sciences, Immunology
• Keywords: CD4-Positive T-Lymphocytes; Ethiopia; HLA-DR Antigens; Humans; Ki-67 Antigen; Leukocytes, Mononuclear; Mycobacterium tuberculosis; Tuberculin; Tuberculosis, Lymph Node; Tuberculosis, Pulmonary

Abstract

Background T cell activation (HLA-DR, CD-38), proliferation (KI-67), and functional (IFN-γ, TNF-α) markers have recently been shown to be useful in predicting and monitoring anti-TB responses in smear positive TB, but previous research did not characterize the activation and proliferation profiles after therapy of smear negative TB. Methodology In this study, we used polychromatic flow cytometry to assess selected PPD-specific T cell markers using fresh PBMC of smear negative and positive pulmonary tuberculosis (PTB) patients, recruited from health facilities in Addis Ababa. Result Levels of activation (HLA-DR, CD38) and proliferation (Ki-67) among total unstimulated CD4 T cells decreased significantly after therapy, particularly at month 6. Similarly, levels of PPD-specific T cell activation markers (HLA-DR, CD-38) were significantly lower in smear positive PTB patients following treatment, whereas a consistent decline in these markers was less apparent among smear negative PTB patients at the sixth month. Conclusion After six months of standard anti-TB therapy, persistent levels of activation of HLA-DR and CD-38 from PPD specific CD4+T cells in this study could indicate that those markers have little value in monitoring and predicting anti-TB treatment response in smear negative pulmonary TB patients in Ethiopian context.