Mycobacterium tuberculosis infection depressed cytotoxic T cells activity owing to decreasing NKG2C and increasing NKG2A expression

Abstract

Cytotoxic T lymphocytes (CTLs) play protective roles in immunity against tuberculosis (TB) infection by strongly inhibiting intracellular mycobacterial growth. In TB infection, the impairing mechanism of CTLs function remains unclear. In this study, we identified that the cytotoxic granule molecules expression levels of perforin (PRF) and granulysin (GNLY) in CD3⁺ and CD8⁺ CTL cells were significantly depressed in TB patients compared to those in healthy donors. The frequencies of T-CTLs, co-expressing granzyme B (GZMB), PRF and GNLY, were obviously decreased in TB patients. Moreover, NKG2C highly expressed in T-CTLs, was an effective activator of cytotoxic activity of CD3⁺ T cells. And, NKG2C⁺CD3⁺ T cells potently inhibited intracellular mycobacterial growth. The proportions of NKG2C⁺ cells in CD3⁺ and CD8⁺ T cells were dramatically decreased in TB patients. Contrarily, NKG2A, an inhibitor of T cells cytotoxic activities, was highly expressed in T-CTLs of CD3⁺ and CD8⁺ T cells in TB patients. Here, we successfully discovered that depressed CTLs activities in TB patients were attributed to low expression of cytotoxic granule molecules and high expression of inhibitory NKG2A receptor, suppression of agonist receptor NKG2C. Thus, NKG2 receptors were potential targets for immunotherapy of tuberculosis, especially for multidrug-resistant tuberculosis.

Keywords: Cytotoxic T cells; Cytotoxic granule molecules; NKG2A; NKG2C; Tuberculosis.