Programmed Death-1 (PD-1), a member of CD28 family is involved in signaling T cells death and negatively regulates T cells function. PD-1 is up-regulated on activated T cells has been shown to play a critical immunoregulatory role in peripheral tolerance, but information on PD-1 expression in human tuberculosis is scarce. It has been shown that chronic exposure to pathogens leads to the up-regulation of PD-1 molecules. In human tuberculosis due to the persistence of Mycobacterium tuberculosis (Mtb.) antigen, aberrant regulation of the PD-1 pathway may influence the diseases manifestation and development of its clinical forms. Present study was to elucidate the expression of PD-1 and its ligands PD-L1/PD-L2 on lmmunocytes among patients with tuberculosis.
A cohort of well characterized Pulmonary Tuberculosis (PTB) patients (n = 24) and healthy control subjects (n = 16) were included to execute the study. Multicolor Flow Cytometry and in-vitro cell culture techniques were employed in the study.
: PD-1 expression was significantly up-regulated on total CD3+ (p < 0.0001), CD4+ (p < 0.0001) and CD8+ (p < 0.0001) T cells derived from tuberculosis patients compared to healthy contacts. Furthermore, this up- regulated expression of PD-1 was also high in natural killer cells (CD3−, CD161+), natural killer T cells (CD3+, CD161+) and CD4+, CD25+ T cells in human tuberculosis patients when compared with healthy subjects. We also observed Mtb. antigen specific up-regulation of PD-1 expression on T cells and increased expression of its ligand PD-L1 on B (CD19+) cells and monocytes (CD14+) as well.
Our result indicates towards the involvement of PD1-PD-L1 inhibitory pathway in human tuberculosis and may be associated with functional impairment of T cells at the disease site. Further study will provide insight into the functional mechanism of PD1-PD-L1 pathway and their influence in host immune response against Mtb.
This observation suggests that PD-1 might be a focal point for therapeutic modulation of T cell responses in tuberculosis.
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