T cells exhaustion, inflammatory and cellular activity markers in PBMCs predict treatment outcome in pulmonary tuberculosis patients

Abstract

Background

Pulmonary tuberculosis (PTB) is a well-known disease caused by Mycobacterium tuberculosis. Its pathogenesis is premised on evasion of the immune system and dampened immune cells activity.

Methods

Here, the transcription pattern of immune cells exhaustion, inflammatory, and cellular activity markers were examined in peripheral blood mononuclear cells (PBMCs) from PTB patients at various stages of treatment. PBMCs were isolated, and RNA extracted. cDNA synthesis was performed, then amplification of genes of interest.

Results

The T cell exhaustion markers (PD-L1, CTLA4, CD244 and LAG3) showed varied levels of expressions when comparing 0 T and 1 T to the other treatment phases, suggesting their potential roles as markers for monitoring TB treatment. IL-2, IFN-g and TNF-a expression at the gene level returned to normal at completion of treatment, while granzyme B levels remained undetectable at the cured stage. At the cured stage, the cellular activity monitors Ki67, CD69, GATA-3, CD8 and CD4 expressions were comparable to the healthy controls. Correlation analysis revealed a significantly strong negative relationship with CD244 expression, particularly between 1 T and 2 T (r = −0.94; p = 0.018), and 3 T (r = −0.95; p = 0.013). Comparing 0 T and 3 T, a genitive correlation existed in PD-L1 (r = −0.74) but statistically not significant, as seen in CTLA4 and LAG-3 expressions.

Conclusion

Collectively, the findings of the study suggest that T-cells exhaustion marker particularly CD244, inflammatory markers IL-2, IFN-g and TNF-a, and cellular activity indicators such as Ki67, CD69, GATA-3, CD8 and CD4 are promising markers in monitoring the progress of PTB patients during treatment.