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

NP Kumar, R Sridhar, D Nair, VV Banurekha… - …, 2015 - Wiley Online Library
NP Kumar, R Sridhar, D Nair, VV Banurekha, TB Nutman, S Babu
Immunology, 2015Wiley Online Library
Type 2 diabetes mellitus (DM) is associated with expanded frequencies of mycobacterial
antigen‐specific CD 4+ T helper type 1 (Th1) and Th17 cells in individuals with active
pulmonary tuberculosis (TB). No data are available on the role of CD 8+ T and natural killer
(NK) cells in TB with coincident DM. To identify the role of CD 8+ 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 …
Summary
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.
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