Effect of standard tuberculosis treatment on naive, memory and regulatory T cell homeostasis in tuberculosis -diabetes co-morbidity.

Kumar, N.P .; Kadar, M.; V ijay, V.; Kornfeld, H .; Babu, S .

Immunology; 2016; 149; 87-97.       

Summary: Perturbations in CD4⁺and CD8⁺ T-cell phenotype and function are hallmarks of tuberculosis–diabetes co-morbidity. However, their contribution to the pathogenesis of this co-morbidity and the effect of anti-tuberculosis treatment on the phenotype of the T-cell subsets is poorly understood. In this study, we examined the frequency of different T-cell subsets in individuals with pulmonary tuberculosis (PTB) with diabetes mellitus (DM) or without coincident diabetes mellitus (NDM) before, during and after completion of anti-tuberculosis chemotherapy. PTB-DM is characterized by heightened frequencies of central memory CD4 + and CD8 + T cells and diminished frequencies of naive, effector memory and/or effector CD4⁺ and CD8⁺ T cells at baseline and after 2 months of treatment but not following treatment completion in comparison with PTB-NDM. Central memory CD4⁺ and CD8⁺ T-cell frequencies exhibited a positive correlation with fasting blood glucose and glycated haemoglobin A1c levels, whereas the frequencies of naive and effector memory or effector CD4⁺ and CD8⁺ T cells exhibited a negative correlation. However, the frequencies of CD4⁺ and CD8⁺ T-cell subsets in individuals with PTB exhibited no significant relationship with bacterial burdens. Finally, although minor alterations in the T-cell subset compartment were observed at 2 months of treatment, significantly decreased frequencies of central memory and significantly enhanced frequencies of naive CD4⁺ and CD8⁺ T cells were observed at the completion of treatment. Our data reveal a profound effect of co-existent diabetes on the altered frequencies of central memory, effector memory and naive T cells and its normalization following therapy.

Keywords: Bacterial; diabetes; T cells

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