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

Microbiol Immunol. 2019 Aug;63(8):316-327. doi: 10.1111/1348-0421.12724. Epub 2019 Jul 26.

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.

Keywords: Th1/Th2 imbalance; cytotoxicity by flow cytometry; high cytotoxic ability; tuberculosis.

MeSH terms

  • Adolescent
  • Adult
  • Antigens, Bacterial / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytokines / blood
  • Cytotoxins / toxicity*
  • Female
  • Flow Cytometry
  • HLA-A Antigens / immunology
  • HLA-B Antigens / immunology
  • HLA-C Antigens / immunology
  • Humans
  • Interleukin-4 / blood
  • Interleukin-8 / blood
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Tuberculosis / immunology*
  • Tuberculosis Vaccines / immunology
  • Tumor Necrosis Factor-alpha / blood
  • Young Adult

Substances

  • Antigens, Bacterial
  • Cytokines
  • Cytotoxins
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-C Antigens
  • IL4 protein, human
  • Interleukin-8
  • Tuberculosis Vaccines
  • Tumor Necrosis Factor-alpha
  • Interleukin-4