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

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.

Multiplex flow cytometry was employed to measure the expression of immune checkpoint (IC) molecules (cytotoxic T-lymphocyte-associated protein-4 [CTLA-4], programmed cell death protein-1 [PD-1], T cell immunoglobulin and mucin-domain containing-3 [TIM-3]) and the proliferation marker Ki67 in MDR-TB (n = 27) and drug-sensitive TB (nondrug resistant [NR]-TB) (n = 51) samples.

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, the expression levels of these IC molecules on T cells decreased along with the anti-TB treatment in MDR-TB patients, and gradually converged to the similar levels of NR-TB subjects.

Our results thus indicate that T cells exhibit more exhausted status in MDR-TB patients which could be reversed after the treatment. These results thus provide an alternative way to ameliorate MDR-TB treatment through improving anti-TB T cell immunity.