Tuberculosis patients display a high proportion of CD8+ T cells with a high cytotoxic potential

Abstract

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) and remains a major cause of morbidity and mortality worldwide. In the host's immune response system, T cells play a critical role in mediating protection against Mtb infection, but the role of CD8+ T cells is still controversial. We evaluated the phenotypical characterization and cytotoxic ability of CD8+ T cells by flow cytometry-based assay. Cytokine levels in serum were measured by multiplex cytokine assay. Our data show that cells from TB patients have an increased percentage of peripheral blood CD8+αβ+ T (p = 0.02) and CD56+CD8+ T (p = 0.02) and a decreased frequency of NKG2D+CD8+ T (p = 0.02) compared with healthy donors. Unlike CD8+ T cells from healthy donors, CD8+ T cells from TB patients exhibit greater cytotoxicity, mediated by HLA class I molecules, on autologous monocytes in the presence of mycobacterial antigens (p = 0.005). Finally, TB patients have a proinflammatory profile characterized by serum high level of TNF-α (p = 0.02) and IL-8 (p = 0.0001), but, interestingly, IL-4 (p = 0.002) was also increased compared with healthy donors. Our data show evidence regarding the highly cytotoxic status of CD8+ T cells in Mtb infection. These cytotoxic cells restricted to HLA-A, B, and C could be used to optimize strategies for designing new TB vaccines or for identifying markers of disease progression.