title: Type 2 diabetes mellitus is associated with altered CD8(+) T and natural killer cell function in pulmonary tuberculosis.
abstract: 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.
authors.affiliation: National Institutes of Health - International Centre for Excellence in Research, Chennai, India; National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Nathella P
authors.initials: NP
authors.lastname: Kumar
authors.forename: Rathinam
authors.initials: R
authors.lastname: Sridhar
authors.forename: Dina
authors.initials: D
authors.lastname: Nair
authors.forename: Vaithilingam V
authors.initials: VV
authors.lastname: Banurekha
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D018655:Lymphocyte Count; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D010641:Phenotype; D011379:Prognosis; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D015415:Biomarkers; D016207:Cytokines
keywords: CD8+ T cells; diabetes; natural killer cells; tuberculosis