Immune profiles of immune checkpoint molecules on peripheral T cells in multidrug-resistant tuberculosis.

Abstract

Background: T cell immunity is impaired due to T cell exhaustion during chronic infection, including infections caused by Mycobacterium tuberculosis (M.tb). However, the immunological characteristics of multidrug-resistant tuberculosis (MDR-TB) patients remain unclear.

Method: Multiparametric flow cytometry was employed to measure the expression of immune checkpoint molecules (CTLA-4, PD-1, TIM-3) and the proliferation marker Ki67 in MDR-TB (n=27) and drug-sensitive TB (NR-TB) (n=51) samples.

Result: We showed that MDR-TB patients exhibited higher percentages of CTLA-4, PD-1, and TIM-3 expressing T cells than NR-TB subjects before anti-TB treatment. Additionally, significantly higher percentages of CTLA-4⁺ PD-1⁺ and CTLA-4⁺ TIM-3⁺ co-expressing T cells were observed in MDR-TB patients when compared to NR-TB patients. Impaired cell proliferation of T cells was detected in MDR-TB patients with more exhaustion status of T cells. Interestingly, In MDR-TB patients, checkpoint-molecule expression on T cells declined during anti-TB treatment and eventually matched NR-TB levels, whereas NR-TB patients showed no significant change.

Conclusion: Our results thus indicate that T cells exhibit more exhausted status in MDR-TB patients which could be reversed after the treatment, which suggests that an additional host-directed treatment might improve the efficacy of anti-TB drug regimens.