The change of PD-1 and CTLA-4 during LTBI and TB reactivation

<b>Background:</b> Tuberculosis (TB) is the most important infectious disease worldwide. However, there are poor understanding for host factors prone to have Mycobacterium tuberculosis infection or the reactivation from latent TB infection (LTBI). In this study, we therefore surveyed the immunomodulation markers during LTBI and active TB and aimed to investigate the association. <b>Methods:</b> We recruited patients with active TB or LTBI and healthy controls. The blood programed death-1(PD-1) and Cytotoxic T Lymphocyte–associated Antigen 4 (CTLA-4) on CD4 lymphocytes were measured using flow cytometry and analyzed. <b>Results:</b> We measured the surface markers of PD-1 and CTLA-4 on CD4 lymphocytes and found PD-1 expression was higher in LTBI subjects than that in active TB or controls. In contrary, CTLA-4 was expressed higher in patients with active TB than that in the other two groups. We defined regulatory T cells (Treg) by positive CD4, CD25, and Foxp3 using flow cytometry. The Treg proportion in PBMCs increased significantly in patients with active TB, which was higher than controls. The PD-1 on Treg cells showed no significant difference among the three groups. In contrary, CTLA-4 on Treg cells was higher in active TB group than that in controls and LTBI group. <b>Conclusions:</b> We preliminarily found that the PD-1 expression were increasing during LTBI status and by contrast, CTLA-4 on CD4 lymphocytes as well as regulatory T cells elevated in TB reactivation. We suggest that the immune modulation pathways of PD-1 and CTLA-4 as well as Treg cells influence different stage of M. tuberculosis infection and needs further investigation for the application in treatment.