T-CELL EXHAUSTION AMONG PULMONARY TUBERCULOSIS CLIENTS IN NORTHERN REGION, GHANA

Abstract

Pulmonary tuberculosis is commonly caused by Mycobacterium tuberculosis. Tuberculosis pathogenesis is based on immune cell depletion and immune system evasion. Peripheral blood mononuclear cells from pulmonary tuberculosis clients were studied for transcription patterns associated with immune cell exhaustion, cellular activity, and inflammatory response at various therapeutic stages of anti-TB therapy at the Chest Clinic of Tamale Teaching Hospital, an experimental study was carried out with twenty-five clients diagnosed with pulmonary tuberculosis and five healthy control clients, making a total of thirty clients. Based on the different stages of the anti-TB treatment, the clients were divided into six groups; namely: newly diagnosed (zero month), intensive phase (≤ 2 months), continuous phase I (>2 & ≤ 5 months), continuous phase II (>5 & ≤ 6 months), completed phased (>6) and healthy control group. Blood specimens were taken from every client in each group. Peripheral blood mononuclear cells were isolated, followed by Ribonucleic acid extraction, then complementary deoxyribonucleic acid synthesis, polymerase chain reaction of the biomarkers of T cells exhaustion, inflammatory cytokines and cellular activities markers. 1% agarose gel electrophoresis was used for the deoxyribonucleic acids bands visualization. The deoxyribonucleic acid gene expression and quantification were carried out using Image J software and Graph pad Prism version 8 statistical tool on the genes of T cell exhaustion, inflammatory cytokine and cellular activities markers. P-values of less than 0.05 were considered statistically significant between the groups. Programme cell death 1 protein, cytotoxic T lymphocytes associated protein 4, CD244 and lymphocyte activated gene 3 in peripheral blood mononuclear cells predict positive pulmonary tuberculosis prognosis during treatment. Correlation analysis suggests CD244 could be a strong marker for monitoring pulmonary tuberculosis treatment outcomes. Transcription of inflammatory cytokines was restored to normal following the initiation of anti-TB treatment. Cellular activity markers CD69, Ki67, Interleukin 7R, Interleukin 15R, GATA-3, CD4 and CD8 were restored to normal and could be used to monitor PTB treatment outcome. The study demonstrated the potential value of T-cell exhaustion markers, specifically PD-L1, inflammatory markers like Interleukin 2, Interferon-gamma and Tumor necrosis factor-a, as well as cellular activity indicators Kiel 67, CD69, GATA-3, CD4, and CD8 blood-based biomarkers can be used in place of sputum in monitoring treatment progress of pulmonary tuberculosis clients.