Type 2 diabetes mellitus is associated with altered CD8(+) T and natural killer cell function in pulmonary tuberculosis

Immunology. 2015 Apr;144(4):677-86. doi: 10.1111/imm.12421.


Type 2 diabetes mellitus (DM) is associated with expanded frequencies of mycobacterial antigen-specific CD4(+) T helper type 1 (Th1) and Th17 cells in individuals with active pulmonary tuberculosis (TB). No data are available on the role of CD8(+) T and natural killer (NK) cells in TB with coincident DM. To identify the role of CD8(+) T and NK cells in pulmonary TB with diabetes, we examined mycobacteria-specific immune responses in the whole blood of individuals with TB and DM (TB-DM) and compared them with those without DM (TB-NDM). We found that TB-DM is characterized by elevated frequencies of mycobacterial antigen-stimulated CD8(+) T cells expressing type 1 [interferon-γ and interleukin-2 (IL-2)] and type 17 (IL-17F) cytokines. We also found that TB-DM is characterized by expanded frequencies of TB antigen-stimulated NK cells expressing type 1 (tumour necrosis factor-α) and type 17 (IL-17A and IL-17F) cytokines. In contrast, CD8(+) T cells were associated with significantly diminished expression of the cytotoxic markers perforin, granzyme B and CD107a both at baseline and following antigen or anti-CD3 stimulation, while NK cells were associated with significantly decreased antigen-stimulated expression of CD107a only. This was not associated with alterations in CD8(+) T-cell or NK cell numbers or subset distribution. Therefore, our data suggest that pulmonary TB complicated with type 2 DM is associated with an altered repertoire of cytokine-producing and cytotoxic molecule-expressing CD8(+) T and NK cells, possibly contributing to increased pathology.

Trial registration: ClinicalTrials.gov NCT01154959.

Keywords: CD8+ T cells; diabetes; natural killer cells; tuberculosis.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Antigens, Bacterial / immunology
  • Biomarkers / blood
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / microbiology
  • Case-Control Studies
  • Cells, Cultured
  • Cytokines / blood
  • Cytokines / immunology*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / immunology*
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / microbiology
  • Lymphocyte Count
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / pathogenicity
  • Phenotype
  • Prognosis
  • Tuberculosis, Pulmonary / blood
  • Tuberculosis, Pulmonary / complications
  • Tuberculosis, Pulmonary / diagnosis
  • Tuberculosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / microbiology


  • Antigens, Bacterial
  • Biomarkers
  • Cytokines

Associated data

  • ClinicalTrials.gov/NCT01154959