Changes of CD27 - and CD38 + in IFN-γ + CD4 + T cells stimulated by Mycobacterium tuberculosis-specific antigen ESAT-6/CFP-10 before and after anti-tuberculosis treatment Running title: CD27 - and CD38 + in IFN-γ+CD4+ T cells for monitoring the efficacy of anti- TB treatment

Background: The aim of the study was to investigate whether the CD27 - CD38 + in IFN-γ + CD4 + T cells stimulated by the specific antigen ESAT-6/CFP-10 could be a potential new therapeutic evaluation indicator for anti-tuberculosis (TB) treatment. Methods: Newly diagnosed active pulmonary TB patients, latent TB infection (LTBI) and healthy controls were enrolled from January 2021 to December 2021. PTB patients were treated by standard anti-TB regimen 2HREZ/4HR. The difference of CD27 - CD38 + in IFN-γ + CD4 + T cells before treatment, 2 months after treatment, and 6 months after treatment were compared. Results: The CD27 - CD38 + in IFN-γ + CD4 + T cells decreased significantly after anti-TB treatment and was comparable with that in LTBI and healthy controls when the 6-month anti-TB treatment course was completed. The decline rate of CD27 - CD38 + between 6 months after treatment and base line was positively correlated with ESR (r=0.766, P<0.0001) and chest CT severity score (r=0.632, P=0.0005). The area under ROC curve of CD27 - CD38 + in distinguish PTB patients before and after treatment was 0.779. Conclusion: The CD27 - CD38 + in ESAT-6/CFP-10 stimulated IFN-γ + CD4 + T cells can well reflect the changes of the disease before and after anti-TB treatment, which is expected to be a potential new therapeutic monitoring biomarker. Clinical Registry number： chiCTR1800019966