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.