Association of T-Cell Profiles With Disease Severity, Drug-Induced Liver Injury, and Treatment Completion in Tuberculosis

Abstract

Background: Tuberculosis (TB) treatment is challenged by a long duration, poor adherence, and the high risk of drug-induced liver injury (DILI). T-cell immunity is essential for anti-mycobacterial defense, but current immune-monitoring methods poorly reflect disease severity and treatment response. Correlations of immune subpopulations with TB severity, DILI, and treatment prognosis remain poorly understood. Methods: Peripheral blood mononuclear cells were collected from confirmed TB patients (n = 40). Multiparameter flow cytometry analysis was used to assess previously defined TB-associated T-cell phenotypes based on the co-expression of cytokines and immune checkpoint molecules following stimulation with two Mycobacterium tuberculosis peptides: culture filtrate protein 10 and early secreted antigenic target 6. Patients were subgrouped by disease severity, DILI, and treatment regimen (16-week short course vs. 24-week standard). Results: Specific subsets (14/124) were found to be associated with disease severity. Notably, six of 14 subsets were positive for programmed death-ligand 1 (PD-L1), indicating its potential role in disease progression. DILI was associated with three interleukin (IL)-21+ subsets (naïve CD4+, memory CD8+, and interferon [IFN]-γ− CD4+ T cells) and IL-17+ memory CD8+ T cells, along with PD-L1+TIM-3+CD4+ T cells (all p < 0.05). The 16-week and 24-week treatment groups showed a significant difference in IFN-γ+ naïve CD8+ T cells at week 16 (p = 0.013), but not at treatment completion (p = 0.393), despite the different durations. Conclusions: This study identifies specific T-cell phenotypes associated with TB severity, DILI, and treatment dynamics, highlighting potential immune markers for disease monitoring and DILI prediction.