Effect of standard tuberculosis treatment on naive, memory and regulatory T-cell homeostasis in tuberculosis-diabetes co-morbidity.
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 coexistent diabetes on the altered frequencies of central memory, effector memory and naive T cells and its normalization following therapy.
National Institutes of Health - NIRT - International Centre for Excellence in Research, Chennai, India.
Nathella P
NP
Kumar
National Institutes of Health - NIRT - International Centre for Excellence in Research, Chennai, India.
Kadar
K
Moideen
Prof. M. Viswanathan Diabetes Research Centre, Chennai, India.
Vijay
V
Viswanathan
University of Massachusetts Medical School, Worcester, MA, USA.
Hardy
H
Kornfeld
National Institutes of Health - NIRT - International Centre for Excellence in Research, Chennai, India.|Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA.
Subash
S
Babu
D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015897:Comorbidity; D048909:Diabetes Complications / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006706:Homeostasis; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000453:epidemiology
D000995:Antitubercular Agents
T cells; bacterial; diabetes